BIOLOGY 

LIBRARY 

G 


SURGICAL 


BACTERIOLOGY 


BY 

1ST.  SENN,  M.D.,  PH.D., 

\\  7      .  7  7 

Professor  of  Surgery  in  Rush  Medical  College,  Chicago,  and  in  the  Chicago  Poly  clinic;  Attending 

Surgeon  to  the  Milwaukee  Hospital,  Consulting  Surgeon  to  the  Milwaukee  County  Hospital 
and  to  the  Milwaukee  County  Insane  Asylum  ;  Honorary  Fellow  College  of  Physicians  of 
Philadelphia;  Permanent  Member  of  the  German  Congress  of  Surgeons;  Corresponding 
Member  Harveian  Society,  London;  Honorary  Member  of  La  Academia 
de  la  Medicina  de  Mexico,  of  the  D.  Hayes  Agnew  Surgical  Society 
of  Philadelphia,  of  the  Ohio  Stale  Medical  Society,  and  of  the 
Minnesota  State  Medical  Society ;    Member  of  the  American 
Surgical  Association,  of  the  American  Medical  Associ- 
ation, of  the  British  Medical  Association,  of  the 
Wisconsin  State  Medical  Society,  and  of  the 
Brainard  Medical  Society,  etc. 


SECOND  EDITION,  THOROUGHLY  REVISED. 


PHILADELPHIA: 

LEA    BROTHERS    &    CO. 

1891. 


BIOLOGY 

LIBRARY 

G 


Entered  according  to  the  Act  of  Congress,  in  the  year  1891,  by 

LEA  BROTHERS  &  CO., 
in  the  Office  of  the  Librarian  of  Congress  at  Washington. 


DORNAN,  PKINTER, 
PHILADELPHIA. 


PREFACE  TO  SECOND  EDITION. 


THE  speedy  exhaustion  of  the  first  edition  is  a  pleasing  evidence 
of  the  interest  the  medical  profession  of  this  country  is  taking  in 
the  subject  of  surgical  bacteriology. 

In  the  preparation  of  the  second  edition  the  author  has  aimed 
to  add  new  facts  illustrative  of  the  relations  of  pathogenic  micro- 
organisms to  the  various  surgical  lesions,  and  eight  new  illustrations 
have  been  inserted  in  the  text  descriptive  of  microbes  not  illustrated 
in  the  first  edition.  The  book  has  also  been  divided  into  chapters, 
which  it  is  hoped  will  prove  useful  for  a  better  classification  of  the 
material  and  for  more  ready  reference. 

N.  SENN. 

CHICAGO,  MARCH,  1891. 


PREFACE  TO  FIRST  EDITION. 


WITHIN  a  few  years  bacteriology  has  revolutionized  surgical 
pathology.  All  wound  complications  and  most  of  the  acute  and 
chronic  inflammatory  lesions  which  come  under  the  treatment  of 
the  surgeon  are  caused  by  microorganisms ;  hence  the  necessity  of 
a  proper  recognition  of  the  importance  of  bacteriology  as  an 
integral  part  of  the  science  and  practice  of  modern  surgery. 

It  has  been  the  endeavor  of  the  author  to  present  the  different 
subjects  contained  in  this  work  in  as  concise  a  manner  as  possible, 
and  at  the  same  time  to  omit  nothing  which  might  be  deemed 
necessary  to  impart  a  fair  knowledge  of  the  subject. 

The  illustrations  are  reproductions  from  Lehrbuch  der  patholo- 
gischen  Anatomic,  by  Prof.  Klebs,  Jena,  1887. 

K  SENK 

MILWAUKEE,  APRIL,  1889. 


LIST   OF   PLATES. 


I.  Facing  page 40 

II.  Facing  page .82 

III.  Facing  page .        .        .112 

IV.  Facing  page 130 

V.  Facing  page  . 158 

VI.  Facing  page 158 

VII.  Facing  page 160 

VIII.  Facing  page 180 

IX.  Facing  page .  200 

X.  Facing  page 202 

XI.  Facing  page 206 

XII.  Facing  page 230 

XIII.  Facing  page  242 


CONTENTS. 


PAGE 

INTRODUCTION ....      17 

CHAPTER  I. 

HEREDITARY  TRANSMISSION  or  MICROBIC  DISEASES         .        .        .19 

CHAPTER  II. 
Do  PATHOGENIC  MICROORGANISMS  EXIST  IN  THE  HEALTHY  BODY  ?      26 

CHAPTER  III. 

SOURCES  OF  INFECTION 29 

. 

CHAPTER  IV. 

LOCALIZATION  OF  MICROBES       .        - 37 

CHAPTER  V. 

ELIMINATION  OF  PATHOGENIC  MICROORGANISMS       ....      56 

CHAPTER  VI. 

ANTAGONISM  AMONG  MICROORGANISMS 68 

CHAPTER  VII. 
INFLAMMATION 71 

CHAPTER  VIII. 

SUPPURATION 79 

CHAPTER  IX. 

GANGRENE  106 


viii  CONTENTS. 

CHAPTER  X. 

PAGE 

SEPTICAEMIA .110 

CHAPTER  XI. 
PY^MIA .124 

CHAPTER  XII. 
ERYSIPELAS 129 

CHAPTER  XIII. 
ERYSIPELOID 139 

CHAPTER  XIV. 
NOMA .     141 

CHAPTER  XV. 
TETANUS 142 

CHAPTER  XVI. 

TUBERCULOSIS       .  .  .  .     156 

CHAPTER  XVII. 
CLINICAL  FORMS  OF  SURGICAL  TUBERCULOSIS 170 

CHAPTER  XVIII. 
ANTHRAX 199 

CHAPTER  XIX. 

GLANDERS  (MALLEUS  HUMIDUS) 207 

CHAPTER  XX. 

ACTINOMYCOSIS  HOMINIS 213 

CHAPTER  XXI. 

GrONORRHCEA 217 

CHAPTER  XXII. 

SYPHILIS 240 

CHAPTER  XXIII. 

ON  THE  ALLEGED  MICROBIC  ORIGIN  OF  TUMORS  249 


SURGICAL  BACTERIOLOGY. 


INTKODUCTION. 

THE  recent  advances  in  surgical  pathology  laid  the  foundation 
for  the  wonderful  achievements  of  modern  surgery.  In  propor- 
tion as  our  knowledge  of  the  etiology  and  pathology  of  the  different 
surgical  lesions  approaches  perfection,  will  surgery  assume  the 
dignity  of  an  exact  science  and  a  true  art.  The  future  progress  in 
surgery  will  be  characterized  by  original  research  in  the  elucida- 
tion of  as  yet  obscure  etiological  and  pathological  questions.  If 
the  nature  of  a  disease  is  well  understood,  rational  suggestions  as 
to  proper  treatment  will  follow  as  a  natural  consequence.  During 
the  last  fifteen  years  there  has  been  more  real  advance  made  in 
surgical  pathology  than  during  twenty  centuries  preceding  them. 
Bacteriology  opened  a  new  era  for  surgical  pathology.  The  knowl- 
edge which  has  accumulated  from  the  bacteriological  investigations 
of  disease  has  opened  new  fields  of  usefulness  for  the  surgeon. 
Many  diseases  heretofore  uselessly  treated  with  drugs  by  the  phy- 
sician are  now  successfully  treated  by  surgical  measures. 

At  this  time,  surgical  pathology  has  almost  become  synonymous 
with  surgical  bacteriology.  Text-books  on  surgical  pathology  of 
only  a  few  years  ago  are  consulted  in  vain  for  information  on 
many  subjects  which  now  attract  universal  attention.  Owing  to 
the  activity  which  is  manifested  everywhere  in  the  investigation 
of  the  microbic  cause  of  disease,  the  many  discoveries  which  are 
being  made  in  rapid  succession,  works  on  pathology  soon  become 
old,  and  are  consigned  to  the  shelves  of  the  antiquarian  almost 
before  they  have  left  the  press.  The  author  of  one  of  the  best 
text-books  on  general  pathology  found  it  necessary  to  prepare  a 
lengthy  appendix  while  the  book  was  going  through  the  press,  in 
order  to  escape  the  criticism  of  the  reviewer  that  it  did  not  repre- 
sent modern  ideas.  We  live  in  an  age  of  independent  thought 
and  investigation.  No  discovery  is  accepted  unchallenged,  and  all 
new  claims  are  subjected  to  the  crucial  test  of  criticism  based  on 
original  research.  Reputation  no  longer  carries  with  it  the  weight 

2 


18  INTRODUCTION. 

of  authority,  unless  the  views  advanced  can  be  corroborated  by  the 
independent  work  of  others. 

In  the  preparation  of  this  work  it  has  been  my  principal  object 
to  gather  from  the  current  medical  literature,  in  compact  form,  the 
result  of  the  best  work  by  the  ablest  men  on  the  various  subjects 
which  will  be  discussed  in  this  book.  In  all  instances  in  which 
the  opinions  of  authors  and  investigators  came  in  conflict  it  has 
been  my  aim  to  represent  their  ideas  without  an  effort  to  harmo- 
nize them.  In  the  consideration  of  disputed  points,  I  have  not 
hesitated  in  stating  my  own  convictions,  which  were  based  either 
upon  the  results  obtained  from  independent  original  research, 
clinical  observation,  or  a  careful  study  of  the  literature  on  the 
subject  at  my  command.  Crookshauk's  Introduction  to  Practical 
Bacteriology,  New  York,  1887,  and  Klebs's  Lehrbuch  der  patho- 
logischen  Anatomie,  I.  Theil,  Jena,  1887,  are  the  only  text-books  I 
consulted.  From  these  I  have  freely  quoted  in  the  descriptions  of 
the  different  microorganisms. 


CHAPTER   I. 

HEREDITARY  TRANSMISSION  OF  MICROBIC  DISEASES. 

THAT  many  of  the  infectious  surgical  diseases  are  hereditary 
has  been  known  for  a  long  time,  and  many  theories  have  been  ad- 
vanced at  different  times  in  the  past  in  explanation  of  their  occur- 
rence. The  modern  views  of  this  subject  may  be  narrowed  down 
to  two  suppositions  :  1.  Transmission  from  parents  to  child  of  a 
predisposition  to  certain  diseases.  2.  Transmission  from  parents 
to  fetus  of  the  essential  cause  of  the  disease.  The  supposed  heredi- 
tary predisposition  is  interpreted  as  meaning  anatomical  or  physio- 
logical defects  in  the  tissues,  which  render  the  organism  susceptible 
to  the  action  of  subsequent  specific  causes.  The  existence  of 
minute  anatomical  defects  of  bloodvessels,  lymphatic  glands  and 
vessels,  connective-tissue  spaces,  etc.,  are  looked  upon  as  conditions 
which  favor  localization  of  floating  microbes,  which  find  their  way 
into  the  body  during  post-natal  life.  An  inherited  defective  vital 
resistance  on  the  part  of  the  tissues  to  the  action  of  pathogenic 
bacteria  is  also  considered  by  many  in  the  light  of  an  hereditary 
influence  in  the  causation  of  disease.  The  conditions  are  recog- 
nized, but  no  satisfactory,  demonstrative,  or  experimental  proofs  of 
their  existence  have  been  furnished,  and  yet  the  immunity  of  some 
animals  to  certain  diseases  cannot  be  explained  in  any  other  way 
than  in  attributing  to  the  tissues  anatomical  or  physiological  prop- 
erties which  protect  the  organism  against  the  action  of  certain 
microorganisms  which,  in  other  animals  not  so  protected,  produce 
a  fatal  disease.  Clinical  experience  has  also  shown  that  a  great 
difference  is  found  among  different  persons  in  reference  to  suscepti- 
bility to  the  same  form  of  infection.  In  many  persons,  for  in- 
stance, inoculation  with  a  pure  culture  of  tubercle  bacilli  would  be 
a  perfectly  harmless  procedure;  in  some  it  would  produce  a  local, 
latent  tuberculosis;  while  in  a  few,  rendered  more  susceptible  to 
this  form  of  infection  by  antecedent  hereditary  or  acquired  causes, 
the  inoculation  of  the  same  number  of  bacilli  would  be  followed 
by  rapid  and  extensive  destruction  of  tissue,  and  death  by  early 
and  diffuse  dissemination.  The  same  can  be  said  of  nearly  all,  if 
not  all  infectious  diseases.  If  their  existence  has  not  been  demon- 
strated, we  are,  nevertheless,  forced  to  recognize  the  influence  of 
certain  as  yet  unknown  conditions  inherent  in  the  tissues,  and 


20  TKANSMISSION    OF    MICEOBIC    DISEASES. 

often  traceable  to  an  hereditary  cause,  which  favor  or  resist  the 
action  of  microbic  causes.  During  the  last  few  years  great  pro- 
gress has  been  made  in  showing  that  hereditary  disease,  in  many 
instances,  at  least,  is  due  to  a  more  direct  cause — the  transmission 
from  mother  to  foetus  of  the  essential  cause  of  the  disease.  This 
method  of  infection  is  not  only  interesting  from  a  scientific  stand- 
point, but  is  of  the  greatest  practical  importance,  alike  to  the  sur- 
geon and  physician,  in  regard  to  prophylaxis,  diagnosis,  and  treat- 
ment of  many  forms  of  disease.  Although  our  knowledge  of  the 
intra-uterine  origin  of  microbic  diseases  is  yet  imperfect,  there  can 
be  no  doubt  that  future  study  and  research  will  clear  up  many 
existing  dark  points,  and  furnish  a  satisfactory  demonstrative  ex- 
planation of  the  direct  and  indirect  hereditary  influences  in  the 
causation  of  disease.  I  shall  in  this  connection  refer  particularly  to 
the  clinical  observations  and  experimental  work  which  tend  to  prove 
the  direct  transmission  of  pathogenic  microbes  from  the  mother  to 
the  foetus. 

1.  CLINICAL  EVIDENCES. — Lebedeff  ("Ueber  die  intra-uterine 
Uebertragbarkeit  des  Erysipels,"  Zeitschrift  fur  Gebwi&hMfe,  B. 
xii.  ~No.  2)  reports  a  case  of  premature  birth  which  occurred  eight 
days  after  the  mother  had  recovered  from  erysipelas.  The  child 
died  ten  minutes  after  birth,  and  the  author  found  Fehleisen's 
streptococcus  in  the  lymphatic  vessels,  in  the  diseased  skin,  and  in 
the  umbilical  cord,  but  not  in  the  placenta.  The  author  believes 
that  the  streptococci  were  transported  from  the  lymphatic  vessels 
of  the  lower  extremities  of  the  mother  through  the  lymphatics  of 
the  uterus  into  the  placental  vessels,  and  from  the  maternal  into 
the  foetal  circulation. 

Curt  Jani  (Lancet,  September  4,  1886,  p.  455)  has  examined  the 
healthy  sexual  organs  of  nine  male  phthisical  patients  for  tubercle 
bacilli.  No  bacilli  were  found,  in  any  of  these,  in  the  semen  from 
the  vesiculse  seminales ;  but,  on  the  other  hand,  in  five  out  of  eight 
cases  a  few  were  found  in  the  testicle,  and  in  four  out  of  six  in  the 
prostate.  The  testicles  appeared  healthy  in  structure.  He  further 
examined  two  women  who  died  of  pulmonary  phthisis,  the  ovaries 
in  both  presenting  negative  results.  In  one  case  of  chronic  pul 
monary  phthisis,  with  extensive  intestinal  tuberculosis,  he  exam- 
ined the  Fallopian  tubes  and  found  tubercle  bacilli.  He  believes 
that  the  tuberculous  virus  can  be  transmitted  from  parents  to 
offspring  in  one  of  two  ways  :  1.  Through  the  semen  of  the  male. 
2.  Through  the  migration  of  bacilli  into  the  uterus  from  the  ab- 
dominal cavity.  Infection  of  the  impregnated  ovum  by  the 
placental  circulation  he  thinks  must  be  unusual,  because  the  exami- 
nation of  the  body  of  a  woman,  five  months  pregnant,  who  died 
from  acute  miliary  tuberculosis,  in  whom  infection  took  place 


CLINICAL    EVIDENCES.  21 

through  the  growth  of  a  caseous  mass  in  a  pulmonary  vein,  showed 
that  there  were  no  bacilli  either  in  the  placental  attachment,  in  the 
lungs,  or  in  any  of  the  organs  usually  the  seat  of  localization  in  the 
embryo.  He,  however,  considers  that  it  is  by  no  means  certain 
that  in  chronic  miliary  tuberculosis  deposits  may  not  form  in  the 
neighborhood  of  the  placenta,  and  thus  infect  the  foetal  organism. 

That  pathogenic  microorganisms  may  exist  in  the  blood  of 
apparently  healthy  mothers  without  doing  any  harm  is  well  illus- 
trated by  children  who  have  been  born  suffering  from  acute  suppu- 
rative  osteomyelitis,  while  the  mother,  through  whose  blood  only 
the  microorganisms  could  have  come,  showed  no  evidences  of 
disease.  Roseubach  reports  such  a  case  in  his  article  on  acute 
osteomyelitis. 

Sangalli  (Virchow  u.  Hirsch's  JahresbericM,  1883,  B.  1,  p.  383) 
found  the  bacilli  of  anthrax  in  the  blood  of  a  foetus  from  a  woman 
who  had  died  of  carbuncle.  In  opposition  to  the  views  of  Golgi 
and  others,  he  affirms  that  the  transmission  of  the  disease  from  the 
mother  to  the  foetus  in  utero  could  only  have  taken  place  by  the 
passage  of  the  bacilli  or  spores  from  the  maternal  to  the  foetal  circu- 
lation through  the  placenta. 

Ahlfeld  and  Marchand  (Centralblatt  f.  Bakteriologie  u.  Para- 
sitenkunde,  No.  14, 1887)  report  the  case  of  a  woman  who  presented 
no  symptoms  of  disease  except  a  moderate  pallor  and  tympanitic 
disteution  of  the  abdomen.  After  a  normal  labor  she  gave  birth  to 
her  second  child ;  eight  hours  after  delivery  the  patient  died  in 
collapse,  for  which  no  explanation  could  be  found.  The  autopsy 
revealed  anthrax  as  the  cause  of  death.  The  child  died  four  days 
after  birth  from  the  same  cause.  The  mother,  as  was  later  ascer- 
tained, contracted  the  disease  in  sorting  horsehair,  and  the  child 
was  infected  directly  through  the  placental  circulation. 

Netter  ("  Transmission  de  la  pneumonic  et  de  Pinfection  pueu- 
monique  de  la  mere  an  foetus/'  Compt.  rend.,  March  9,  1889) 
reports  a  carefully -observed  case  of  the  direct  transmission  of  the 
diplococcus  of  pneumonia  from  mother  to  foetus.  The  mother  was 
a  Vl.-para,  pregnant  eight  months  when  she  was  attacked  with 
croupous  pneumonia,  which  terminated  on  the  seventh  day  in 
recovery.  On  the  ninth  day  after  the  attack  she  was  delivered  of  a 
living  child.  The  child  died  on  the  fifth  day  after  birth.  The 
autopsy  revealed  lobar  pneumonia,  involving  the  right  upper  lobe, 
double  fibrinous  pleuritis,  pericarditis,  suppurative  meningitis,  and 
otitis  media  on  both  sides.  Bacteriological  examination  of  the  dif- 
ferent inflammatory  products,  as  well  as  of  the  blood  taken  from  the 
left  ventricle,  showed  the  presence  of  Frankel's  diplococcus  of 
pneumonia. 


22  TRANSMISSION    OF    MICROBIC    DISEASES. 

2.  EXPERIMENTAL  PROOF. — Bellinger  was  the  first  to  assert 
that  the  bacillus  of  anthrax  could  pass  from  mother  to  foetus  through 
the  placenta. 

Strauss  and  Chamberland  ("Sur  le  passage  de  la  bacteridie 
charbonneuse  de  la  mere  au  foetus,"  Gazette  kebdom.  de  Med.  et  de 
Chir.,  1883,  No.  10)  experimented  on  guinea-pigs  to  prove  that 
intra-uterine  transmission  of  anthrax  from  mother  to  offspring  is 
possible.  Gravid  animals  were  inoculated  and  the  foetuses  examined 
immediately  after  death.  Blood  taken  from  the  cavities  of  the 
heart  and  the  liver,  examined  under  the  microscope,  never  showed 
bacilli.  Cultivation  experiments  were  made  with  the  foetal  blood 
in  veal  bouillon,  and  these  demonstrated  that  in  some  instances  the 
blood  of  all  foetuses  from  the  same  mother  contained  bacilli;  some- 
times all  cultures  remained  sterile ;  while  in  some  the  blood  of  only 
one  foetus  would  yield  a  positive  result.  From  these  experiments 
the  authors  came  to  the  conclusion  that  the  tissues  of  the  placenta 
offer  no  insurmountable  obstacle  to  the  passage  of  the  bacillus  of 
anthrax  from  the  maternal  into  the  foetal  circulation. 

Max  Wolff  ("Ueber  Yererbung  von  Infections-  krankheiten," 
Virchow's  Archiv,  B.  112,  pp.  136-202)  has  studied  the  subject  of 
intra-uterine  transmission  of  infective  diseases  by  a  series  of  carefully- 
conducted  experiments.  lie  worked  with  cultures  of  anthrax  bacilli 
and  examined  the  blood  and  internal  organs  of  the  foetuses  under 
the  microscope,  and  tested  their  sterility  by  cultivation  and  inocula 
tion  experiments.  The  pregnant  animals  which  were  inoculated 
with  a  pure  culture  of  anthrax  bacilli  manifested  symptoms  of  the 
disease  in  from  thirty-six  hours  to  three  days.  The  blood  and  inter- 
nal organs  of  29  foetuses  contained  no  bacilli,  as  was  shown  by  most 
careful  microscopical  examination,  after  single  and  double  staining. 

The  placenta  in  each  instance  contained  numerous  bacilli,  while 
the  villi  of  the  chorion  showed  no  trace  of  them.  From  these 
29  foetuses  156  cultivation  experiments  were  made  with  tissue  from 
the  kidney,  liver,  and  lungs,  and  of  this  number  a  positive  result 
was  obtained  in  only  6.  14  guinea-pigs  and  16  white  mice  were 
inoculated  with  foetal  tissue,  with  the  result  that  in  only  3  cases  was 
the  disease  transmitted  in  this  manner.  The  author  is  inclined  to 
the  belief  that  the  successful  cultivations  and  inoculations  were  due 
to  contamination  with  the  maternal  tissues.  He  affirms  that  the 
placenta  constitutes  an  impervious  barrier  to  the  passage  of  micro- 
organisms from  the  maternal  into  the  foetal  circulation. 

'Koubassoff  (Gentralblatt  f.  d.  med.  Wissenschaften,  Jan.  6,  1886) 
came  to  more  positive  results  in  his  experiments  with  anthrax 
bacillus.  In  all  of  his  experiments,  the  foetuses  of  the  infected 
animals  contracted  the  disease  in  utero.  He  also  found  that 
time  played  an  important  part  as  far  as  the  number  of  bacilli  in 


EXPERIMENTAL    PROOF.  23 

the  foetus  was  concerned,  as  the  longer  the  period  which  inter- 
vened between  the  inoculation  and  the  death  of  the  mother,  the 
more  numerous  were  the  bacilli  in  the  foetal  organs,  showing  that 
the  migration  of  microbes  from  the  maternal  to  the  foetal  side  of 
the  placenta  is  continuous.  Inoculation  experiments  with  the 
attenuated  virus  proved  that  iutra-uterine  transmission  took  place 
more  slowly.  Inoculation  of  gravid  animals  with  a  very  strong 
anthrax  vaccine  nearly  always  proved  fatal  to  the  foetus.  Prophy- 
lactic vaccination  of  the  foetus  through  the  mother  proved  insuf- 
ficient against  subsequent  inoculations  with  the  attenuated  virus. 
In  another  paper  the  same  author  (Centralblatt /.  Gyndkologie,  Dec. 
5,  1885)  has  published  some  important  observations  on  the  same 
subject,  made  in  Pasteur's  laboratory,  in  which  he  showed  that  in 
pigs  the  microbes  of  malignant  oedema  and  tuberculosis  pass  directly 
from  mother  to  offspring  through  the  placenta. 

Kroner  ("  Ueber  den  gegenwartigen  Stand  der  Frage  des  Ueber- 
ganges  pathogeuer  Microorgauismen  von  Mutter  auf  Kind/7  Bres- 
lauer  drzt.  Zeitschr.,  1886,  No.  11)  made  his  experiments  on  rabbits 
with  the  bacteria  of  sepsis.  The  results  obtained  were  not  con- 
stant. In  all,  six  rabbits  were  inoculated  at  different  stages  of 
gestation.  In  the  blood  of  the  foetuses  no  bacteria  could  be  found. 
Inoculation  with  the  blood  of  the  foetuses  yielded,  among  a  num- 
ber of  negative,  four  positive  results.  After  a  careful  considera- 
tion of  the  subject,  based  upon  his  own  experience  and  the  obser- 
vations of  others,  he  came  to  the  conclusion  that  a  number  of 
microbic  diseases  are  communicable  from  mother  to  child  through 
the  placeutal  circulation. 

One  of  the  strongest  evidences  of  direct  transmission  of  patho- 
genic microbes  from  mother  to  foetus  through  the  placental  circu- 
lation, has  been  furnished  by  Johne  (Lancet,  March  6,  1886).  An 
eight  months'  foetus  was  taken  from  a  cow  the  subject  of  advanced 
tuberculosis.  No  tuberculous  products  were  found  in  the  placenta 
or  the  uterus ;  but  in  the  lower  lobe  of  the  right  lung  of  the  foetus 
a  nodule,  the  size  of  a  pea,  was  detected,  containing  four  caseous 
centres.  The  bronchial  glands  were  the  seat  of  tubercular  adenitis. 
The  liver  contained  numerous  miliary  tubercles.  All  the  lesions 
presented  under  the  microscope  the  characteristic  histological 
structure  of  tubercle. 

Levy  (Journal  des  Connaissances  Medicale,  Janvier,  1890,  abstract 
in  American  Journal  Medical  Sciences,  August,  1890)  reports  the 
case  of  a  woman,  aged  thirty  years,  who  had  died  from  double 
fibriuous  pneumonia,  complicated  by  pleurisy  and  pericarditis.  By 
aspiration  sero-purulent  fluid  was  removed  from  the  thoracic  cavities. 
This  fluid  gave  cultures  showing  the  diplococcus  of  Frankel- 
Weichselbaum  ;  inoculations  from  this  fluid  showed  the  presence 


24  TRANSMISSION    OF    MICROBIC    DISEASES. 

and  potency  of  the  germ.  This  woman's  child  was  born  thirty- 
six  hours  before  its  mother's  death,  and  died  two  days  later  from 
hemorrhagic  catarrhal  pneumonia  and  fibrinous  lobar  pneumonia. 
Autopsy  demonstrated  the  infectiousness  and  that  it  had  persisted 
at  least  thirty-six  hours  before  the  child  was  born.  Cultures  made 
with  fluids  removed  from  the  left  heart  ventricle  and  from  the 
right  lung,  demonstrated  the  presence  of  the  diplococcus;  the 
microorganisms  were  especially  numerous  in  the  blood.  The  con- 
clusions are  that  the  child  was  infected  from  the  mother's  pneu- 
monia. 

That  syphilis  is  a  microbic  disease  can  no  longer  be  doubted, 
and  that  it  is  one  of  the  diseases  which  is  most  frequently  trans- 
mitted from  parents  to  offspring  is  well  known.  Some  interesting 
observations  have  recently  been  made  on  the  etiology  and  trans- 
missibility  of  syphilis  by  Disse  and  Taguchi,  of  Japan  (Qentralblatt 
f.  Gyndkologie,  1888,  No.  11),  and  if  future  research  should  cor- 
roborate their  claims,  their  researches  will  constitute  an  important 
contribution  to  our  knowledge  of  the  heredity  of  this  disease. 
They  discovered  in  syphilitic  lesions,  isolated,  and  cultivated  from 
them,  a  diplococcus.  With  a  pure  culture  of  this  microbe  they 
inoculated  gravid  dogs,  and  found  that  the  microbe  permeated  the 
placental  tissues,  and  entered  directly  into  the  circulation  of  the 
embryo.  The  pups  suffered  from  all  the  characteristic  lesions  of 
hereditary  syphilis  as  observed  in  man.  The  lesions  commonly 
found  were  pneumonia,  disease  of  the  liver,  bones,  and  kidneys. 
In  all  of  these  organs  the  same  diplococcus  was  found  as  was  used 
in  the  inoculation  experiments. 

Eomeo  Mangeri,  of  Catania,  believes  that  direct  transmission  of 
microbes  from  mother  to  foetus  through  normal  placental  vessels  is 
impossible.  As  the  result  of  an  extensive  study  of  the  literature 
of  the  subject  and  of  original  experiments,  he  has  come  to  the 
conclusion  that  no  formed  elements  naturally  pass  out  of  the 
mother's  blood  into  the  foetal  circulation.  Cinnabar,  Indian  ink, 
carmine,  and  other  finely-divided  pigment  materials  were  injected 
into  the  jugular  vein's  of  animals  advanced  in  pregnancy,  but  in 
no  case  could  any  trace  of  the  substance  employed  be  found  in  the 
foetus.  According  to  his  belief,  passage  of  formed  elements  can 
only  occur  when  the  placenta  becomes  diseased  by  inflammation, 
or  is  partially  detached  so  that  the  walls  of  the  villi  are  destroyed. 
Only  under  this  condition  he  maintains  can  pathogenic  microorgan- 
isms be  transmitted  from  the  mother  into  the  foetal  blood. 

Most  all  authors  agree  that,  when  extravasations,  or  other  patho- 
logical processes  occur  in  the  placental  attachment,  the  direct  en- 
trance of  microbes  from  the  mother  into  the  foetal  circulation  is 
not  only  a  possible,  but  a  probable  occurrence.  Abnormality  in 


EXPERIMENTAL    PROOF.  25 

the  placental  circulation  must,  therefore,  be  recognized  as  a  condi- 
tion which  favors  the  transmission  of  microorganisms  from  mother 
to  fetus. 

All  of  the  foregoing  observations  and  experiments  furnish  sub- 
stantial proof  that  in  some  infectious  diseases  heredity  is  traceable  to 
direct  transmission  of  the  specific  microbes  floating  in  the  circula- 
tion of  the  mother  to  the  foetus,  through  the  thin  wall  which  sepa- 
rates the  maternal  from  the  foetal  blood.  It  is  no  more  difficult  to 
explain  the  migration  of  microbes  through  such  a  thin  septum 
than  their  transportation  from  one  tissue  to  another,  and  from 
organ  to  organ  in  other  parts  of  the  body,  more  especially  as  the 
anatomical  conditions  for  mural  implantation  in  the  placental 
vessels  are  most  favorable  for  such  an  occurrence. 


CHAPTEE    II. 

DO  PATHOGENIC  MICROORGANISMS  EXIST  IN  THE 
HEALTHY  BODY? 

IT  still  remains  a  disputed  question  whether  pathogenic  micro- 
organisms can  exist  in  the  body  without  giving  rise  to  disease.  It 
has  been  definitely  ascertained  by  experimental  research  that  many 
of  the  pathogenic  germs  are  harmless  as  long  as  they  remain  in  the 
circulating  blood,  and  that  their  specific  pathogenic  action  only 
becomes  evident  after  localization  takes  place  in  some  part  of  the 
body,  in  a  soil  prepared  by  injury,  or  disease,  for  their  arrest  and  mul- 
tiplication. It  has  also  been  definitely  settled  by  clinical  experience 
that  pathogenic  spores  may  remain  in  the  healthy  body,  in  a  latent 
condition,  for  an  indefinite  period  of  time,  until  by  some  accidental 
pathological  changes  the  tissues  in  which  they  may  exist  have  been 
prepared  for  their  growth.  Numerous  experiments  will  be  cited 
elsewhere,  in  which  injections  of  pure  cultures  directly  into  the 
circulation  produced  no  ill  effects  in  healthy  animals,  but  when 
previous  to  the  injection,  or  soon  after,  an  injury  was  inflicted  in 
some  part  of  the  body,  localization  occurred  at  the  seat  of  trauma, 
and  in  the  culture  soil  thus  prepared  the  microbes  produced  their 
specific  pathogenic  effects.  From  these  remarks  it  is  reasonable  to 
assume  that  pathogenic  germs  may  exist  in  the  healthy  body  with- 
out necessarily  giving  rise  to  disease,  especially  if,  as  is  well  known, 
they  are  being  constantly  eliminated  through  the  excretory  organs. 
Some  of  the  arguments  for  and  against  this  theory  will  now  be 
introduced. 

Fodor  (u  Bacterien  im  Blute  lebeuder  Thiere,"  Arohivf.  Hygiene, 
B.  iv.  p.  129)  introduced  directly  into  the  circulation  of  rabbits 
pathogenic  bacteria,  in  order  to  study  their  effects  on  the  tissues 
and  manner  of  elimination.  As  a  rule,  he  found  that  they  had 
completely  disappeared  from  the  blood  after  twenty-four  hours. 
No  culture  experiments  were  made  less  than  four  hours  after  inocu- 
lation. He  believes  that  the  microbes  are  removed  by  the  red  cor- 
puscles, or  that  they  are  digested  by  the  leucocytes.  He  affirms 
that,  as  a  rule,  pathogenic  germs  are  not  present  in  the  healthy 
organism,  as  he  found  the  blood  of  healthy  rabbits,  without  excep- 
tion, sterile ;  and  only  in  exceptional  cases  was  he  able  to  demon- 
strate the  presence  of  bacteria  in  animals  killed,  even  where  the 
examination  was  postponed  until  putrefaction  had  set  in. 


PATHOGENIC    MICRO-OKG ANISMS    IN    THE    BODY.       27 

Zahor  ("  Ueber  das  Vorkommen  von  Spaltpilzen  im  normalen 
thierischeu  Korper,"  Wiener  med.  Jahrbilcher,  p.  343,  1886)  exam- 
ined the  blood,  testicle,  heart,  and  spleen  of  a  healthy  rabbit,  and 
found  in  fresh  as  well  as  in  hardened  sections,  after  staining  with 
methyl-violet,  cocci,  and  here  and  there  rods.  The  same  examina- 
tions with  like  results  were  made  on  the  organs  of  a  young  cat. 
Under  strict  antiseptic  precautions  he  removed  a  testicle  from  an- 
other healthy  animal,  and  embedded  it  at  once  in  paraffin,  which, 
under  the  microscope,  was  also  seen  to  contain  bacteria. 

Bizzozero  (Virchow's  Jahresbericht,  1887,  B.  1,  p.  283)  could 
not  detect  bacteria  of  any  kind  in  animals  soon  after  birth,  but 
in  the  lymph  follicles  of  the  vermiform  process  in  healthy  rabbits 
he  found  numerous  bacteria  which  could  be  readily  stained  with 
Gram's  solution,  and  which,  in  form  and  size,  corresponded  with 
the  schizomycetes  which  are  always  contained  in  the  intestinal  con- 
tents of  these  animals.  The  microbes  were  seen  mostly  in  the  pro- 
toplasm of  cells,  a  condition  which  would  indicate  that  they  are 
transferred  from  the  intestinal  canal  into  the  closed  lymph  follicles 
through  the  medium  of  migrating  cells. 

Hauser  (Vorkommen  von  Microorganismen  im  lebenden  Gewebe 
gesunder  Thiere,  Archivf.  experimentelle  Pathologic  und  Pharma- 
cologie,  B.  xx.  pp.  162-202)  has  made  a  number  of  carefully-con- 
ducted experiments  to  show  that  no  microbes  exist  in  healthy  animals. 
The  experiments  consisted  principally  in  procuring  tissues  prone  to 
fermentation,  as  parts  of  internal  organs,  blood,  etc.,  and  protecting 
them  against  infection  from  without.  He  kept  the  specimens  in 
rarefied  air,  in  filtered  air,  hydrogen,  oxygen,  carbonic  acid  gas, 
and  water,  and  in  various  artificial  culture  soils,  at  a  temperature 
favorable  to  putrefaction,  but  in  all  instances  in  which  the  speci- 
mens remained  nncontaminated  no  putrefactive  changes  were  ob- 
served. By  this  method  he  believed  he  was  able  to  demonstrate 
that  tissues  taken  from  healthy  animals  immediately  after  death 
contained  no  putrefactive  bacteria,  since  it  is  well  known  that  if  the 
specimens  were  not  perfectly  sterile  putrefaction  would  have  taken 
place.  The  author  did  not  only  appear  to  demonstrate  that  living 
tissues  contained  no  microorganisms,  but  he  also  ascertained  that 
the  preserved  sterile  organs  in  time  underwent  a  sort  of  regressive 
metamorphosis  similar  to  that  which  takes  place  in  the  body  in  the 
absence  of  microorganisms,  and,  what  is  of  especial  interest,  that 
the  products  of  such  processes  of  resolution  possess  no  poisonous 
properties  whatever. 

Fodor  (Deutsche  med.  Wochenschrift,  1887)  has  shown  that  the 
power  of  the  blood  to  destroy  bacteria  is  not  diminished  by  a  mod- 
erate degree  of  anemia,  but  is  lessened  when  diluted  with  water, 
as  when  this  is  done  the  microbes  are  destroyed  more  slowly,  and 


28      PATHOGENIC    MICRO-OEG ANISMS    IN    THE    BODY. 

with  greater  difficulty.  Anthrax  bacilli  injected  in  large  quanti- 
ties directly  into  the  circulation  disappeared  from  the  blood  in  four 
hours ;  but  within  twenty  to  twenty-four  hours  they  reappeared 
and  the  animal  died.  As  the  bacilli  disappeared  from  the  circulat- 
ing blood  localization  in  internal  organs  took  place,  and  their 
reappearance  in  the  circulation  only  implies  an  enormous  increase 
in  number,  and  invariably  resulted  in  the  death  of  the  animal. 
Anthrax  is  a  blood  disease ;  but  the  blood  is  rather  the  protector 
of  the  organism  against  pathogenic  microbes. 

Watson  Cheyne("On  Suppuration  and  Septic  Diseases,"  British 
Medical  Journal,  March  3,  1888)  found  in  his  experiments  on  the 
presence  or  absence  of  microorganisms  in  the  living  tissues  that, 
while  germs  were  absent  when  the  animal  was  in  a  good  state  of 
health,  yet  if  the  vitality  of  the  animal  was  depressed,  say,  by 
administering  large  doses  of  phosphorus  for  some  time,  organisms 
could  be  found  at  times  in  the  blood  and  tissues  of  the  body. 
Again,  it  has  been  found  that,  while  some  microorganisms  when 
introduced  into  the  living  body  in  small  number,  disappear  after  a 
short  time,  when  a  large  quantity  of  the  cultivation  is  introduced 
the  tissues  of  the  body  are  injured  by  the  preexisting  ptomaines 
and  the  germs  retain  their  vitality  and  often  produce  their  specific 
pathogenic  effects.  Diminution  of  the  force  of  the  circulation  also 
plays  an  important  part  in  the  production  of  microbic  diseases. 
Thus,  according  to  Cornil,  a  septic  nephritis  is  readily  produced  by 
ligating  the  renal  arteries  for  some  time  and  then,  after  removal  of 
the  ligature,  injecting  pyogenic  organisms  into  the  blood.  Heubner 
made  the  same  experiment  on  the  bladder  and  found  that  by  inter- 
rupting the  arterial  supply  for  a  certain  time  coagulation-necrosis 
occurred  in  the  protoplasm  of  the  epithelial  cells  which  furnished 
the  most  favorable  conditions  for  septic  infection  when  septic 
germs  were  introduced  into  the  circulation. 

Coruil  also  found  that  if  a  simple  nephritis  is  induced  by  the 
administration  of  cantharides,  the  pathological  conditions  thus  pro- 
duced furnished  the  most  favorable  soil  for  septic  nephritis,  when 
the  animal  was  infected  with  septic  germs. 


CHAPTEK  III. 

SOURCES  OF  INFECTION. 

PETTENKOFEB  divided  the  pathogenic  bacteria  into  two  classes 
— the  endo-  and  eeto-genous.  Under  the  former  head  were  classified 
all  bacteria  which  were  supposed  to  have  an  endogenous  origin, 
while  the  ectogenous  variety  included  all  bacteria  which  enter  the 
organism  from  without.  Syphilis  and  tuberculosis  were  regarded 
as  endogenous  processes,  but  since  it  has  been  made  possible  to 
cultivate  the  tubercle  bacilli  outside  of  the  body  and  to  produce 
with  them  typical  tubercular  lesions,  this  disease  cannot  be 
attributed  any  longer  to  an  endogenous  origin,  and  it  will  not  be 
long  before  future  research  will  transfer  syphilis  from  the  endoge- 
nous to  the  ectogenous  variety  for  the  same  reason.  Even  in 
the  most  marked  cases  of  so-called  auto-infection  the  microbes 
must  have  entered  the  organism  at  some  previous  time  from  with- 
out, and  all  such  affections  are  in  every  sense  of  the  word  ectoge- 
nous processes.  In  surgery  it  is  of  special  importance  that  the 
endogenous  origin  of  infective  diseases  should  be  no  longer  recog- 
nized, and  that  their  causes  should  always  be  sought  for  outside  of 
the  body. 

Bacteriology  has  rendered  the  term  miasma  obsolete.  All  infec- 
tive diseases  are  now  traced  to  an  organic  contagium.  All  infective 
diseases  in  the  strict  sense  of  the  word  are  contagious,  as  they  can 
only  arise  by  the  entrance  of  pathogenic  microbes  from  without, 
and  this  can  only  take  place  if  they  are  brought  in  contact  with 
an  absorbing  surface.  Of  all  substances  which  serve  as  a  carrier 
of  microbes,  the  atmospheric  air  is  the  most  important,  because  it 
is  present  everywhere  and  no  one  can  exclude  himself  from  it.  In 
a  dry  state,  pathogenic  germs  move  with  the  currents  of  air  and 
attach  themselves  again  to  the  solid  or  fluid  substances  with  which 
they  come  in  contact.  Although  most  of  the  microbes  under 
ordinary  circumstances  do  not  reproduce  themselves  outside  the 
body,  their  resistance  to  heat  and  cold,  moisture  and  dryness,  is  so 
great  that  they  retain  their  disease-producing  qualities  often  for  an 
indefinite  period  of  time,  and  after  their  entrance  into  the  body 
and  meeting  with  a  proper  nutrient  medium  they  exert  their  spe- 
cific pathogenic  effects. 

Sternberg  (u  The  Thermal   Death-point  of  Pathogenic  Organ- 


30  SOUECES    OF    INFECTION. 

isms,"  American  Journal  Med.  Sciences,  vol.  94,  p.  146)  has  found 
by  a  series  of  very  interesting  experiments  that  different  pathogenic 
germs  possess  varying  degrees  of  resistance  to  heat.  The  following 
were  his  results  in  studying  the  microorganisms  which  more  par- 
ticularly interest  the  surgeon.  The  time  of  exposure  was  ten 
minutes,  unless  otherwise  indicated  by  figures  in  parentheses : 

Fahrenheit. 

Bacillus  anthracis  (Chaveau)       .         .         .  129.2° 

Bacillus  anthracis  spores     .         .         .         .         .  212.0 

Bacillus  tuberculosis  (Schill  and  Fischer) .         .  212.0  (4  m.) 

Staphylococcus  pyogenes  aureus         .         .         .  136.4 

Staphylococcus  pyogenes  albus  .         .         .  143.6 

Staphylococcus  pyogenes  citreus         .         .         .  143.6 

Streptococcus  erysipelatosus        ....  129.2 

Gonococcus          .......  140.0 

Of  course,  the  same  difference  of  resistance  to  cold  and  other 
destructive  influences  must  exist  among  them. 

The  spores  possess  still  greater  resisting  powers,  and  conse- 
quently, in  places  where  the  destructive  influences  are  sufficiently 
severe  to  destroy  microbes,  infection  may  still  take  place  from  this 
source. 

J.  Geppert  ("  Zur  Lehre  von  den  Antisepticis,"  Berl.  klin. 
Wochenschrift,  Sept.  9, 1889)  while  making  the  experiments  for  the 
purpose  of  verifying  the  statements  of  Woronzoff  and  others,  that 
the  spores  of  the  bacillus  anthracis  are  rendered  harmless  by  im- 
mersion in  a  1  to  10,000  solution  of  sublimate  for  fifteen  minutes, 
and  by  a  1  to  2000  solution  in  one  minute,  found  a  source  of  fal- 
lacy in  their  method.  This  consists  in  impregnating  a  thread  with 
the  spores  and  immersing  it  in  the  antiseptic  solution  for  the  desired 
time,  and  after  washing  it  in  alcohol  or  water,  using  it  to  inoculate 
nutrient  media  or  animals,  the  extreme  difficulty  of  removing  all 
traces  of  the  chemical  used  becomes  apparent,  while  its  importance 
is  shown  by  the  statement  of  Koch,  that  the  presence  of  sublimate 
in  the  strength  of  1  to  100,000  will  retard  the  growth  of  anthrax 
spores.  Geppert's  method  consists  in  using  a  suspension  of  spores 
in  distilled  water,  which  is  then  filtered  through  glass  wool  until 
the  liquid  is  perfectly  clear.  After  subjecting  the  spores  for  a  defi- 
nite length  of  time  to  the  action  of  the  antiseptic  he  used  some 
indifferent  chemical  to  precipitate  the  antiseptic.  In  the  case  of 
sublimate  he  used  ammonium  sulphide.  He  made  inoculations  with 
spores  exposed  to  the  action  of  the  sublimate  before  and  after  pre- 
cipitation. When  he  used  spores  exposed  to  the  action  of  a  subli- 
mate solution  1  to  1000,  without  precipitation,  he  obtained  cultures 
in  all  cases  after  an  exposure  for  three  minutes,  once  after  seven 
minutes,  also  after  ten  minutes.  In  using  spores  of  solutions  where 


SOURCES    OF    INFECTION.  31 

precipitation  had  been  practised  he  always  obtained  numerous  and 
large  colonies  after  exposure  to  the  action  of  the  antiseptic  for 
fifteen  minutes,  less  after  thirty  minutes,  and  very  few  after  an 
hour's  exposure,  and  only  in  exceptional  cases  were  positive  results 
obtained  after  action  of  the  antiseptic  for  two  or  three  hours,  and 
with  one  exception  never  after  seven  to  twenty-four  hours'  expo- 
sure. Combinations  with  other  antiseptics  had  no  retarding  effect. 
From  his  experiments  he  was  led  to  conclude  that  spores  exposed 
for  some  time  to  a  sublimate  solution  will  not  grow  upon  a  soil 
containing  the  antiseptic  in  a  very  diluted  form,  while  spores  simi- 
larly treated  will  not  grow  upon  a  soil  upon  which  spores  not  so 
treated  will  grow. 

By  improved  methods  of  investigation  it  has  recently  been  made 
possible  not  only  to  demonstrate  the  presence  of  microbes  in  the 
atmospheric  air,  but  also  to  prove  their  identity  and  approximately 
to  determine  their  number  in  a  certain  volume  of  air.  From  the  inge- 
nious experiment  made  by  Miquel  ("  Des  bacteries  atmospheriques," 
Comptes  rend.,  t.  91,  No.  1)  it  appears  that  the  air  picks  up  in  its  pas- 
sage across  the  city  of  Paris  in  the  course  of  half  an  hour  three  times 
the  number  of  microbes  it  contains  when  blowing  over  the  country. 
On  the  basis  of  a  series  of  carefully-made  observations  to  determine 
the  number  of  microbes  which  a  certain  volume  of  air  contains  at 
different  seasons  of  the  year,  he  found  that  a  cubic  centimetre  of 
air  contains  on  an  average  two  hundred  spores  of  bacteria.  During 
the  summer  such  a  volume  of  air  often  contains  as  many  as  1000, 
while  during  the  cold  months  of  winter  it  contains  as  few  as  4  or  5. 
In  rooms  with  no  draft  of  air,  it  required  30  to  50  litres  of  air 
for  a  successful  inoculation  of  a  sterile  culture  substance.  In 
Miquel's  laboratory  5  litres  were  found  sufficient,  while  1  litre  of 
air  taken  from  the  subterranean  channels  in  Paris  produced  the 
same  effect.  In  a  cubic  yard  of  air  taken  from  the  wards  of  a  long- 
used  hospital  he  found  as  many  as  90,000  microbes.  This  same 
observer  has  shown,  and  others  have  confirmed  it,  that  sea  air  con- 
tains scarcely  any  of  these  microorganisms,  and  that  mountain 
heights  are  as  nearly  free  from  them  for  obvious  reasons. 

In  a  recent  communication  to  the  Royal  Society,  Dr.  Frankland 
described  a  new  method  of  examining  air  for  microorganisms.  It 
consists  in  aspirating  a  known  volume  of  air  through  a  glass  tube 
containing  two  sterile  plugs  of  glass  wool  alone,  or  of  glass  wool 
with  fine  glass  powder,  etc.,  the  first  plug  being  more  pervious  than 
the  second.  These  plugs  are  then  transferred  to  sterilized  liquid 
gelatine-peptone,  thoroughly  agitated  with  it,  and  then  the  gelatine 
is  congealed,  so  as  to  form  an  even  film  over  the  inner  surface  of 
the  flask.  The  number  of  colonies  which  develop  are  then  counted. 
Klebs  has  devised  a  very  ingenious  but  complicated  apparatus  for 


32  SOURCES    OF    INFECTION. 

filtering  a  measured  quantity  of  atmospheric  air  directly  upon  cul- 
ture plates,  which  he  used  in  prosecuting  his  researches  on  the 
microbe  of  malaria  in  the  vicinity  of  Rome.  Tyndall  has  shown 
that  floating  microbes  not  only  enter  our  bodies,  but  are  arrested  and 
retained  in  them,  by  transmitting  a  beam  of  electric  light  through 
air  before  and  after  it  has  been  respired,  which  has  demonstrated 
that,  however  populated  before,  it  is  entirely  free  from  organic  and 
inorganic  particles  after  it  has  once  passed  through  our  lungs. 

At  a  recent  meeting  of  the  Academy  of  Sciences  of  Paris, 
Strauss  ("  Sur  1'absence  de  microbes  dans  Pair  expire,"  La  Semaine 
Medicale,  1887,  No.  49)  reported  a  series  of  bacteriological  experi- 
ments upon  expired  air.  He  confirms  the  result  arrived  at  by 
Tyndall,  that  expired  air  is  optically  pure,  and  adds  the  further 
fact  that  it  contains  no  microbes.  Gaucher,  Charrin,  and  Karth 
examined  the  expired  air  in  phthisical  patients  and  failed  to  find 
bacilli.  The  bronchial  tubes  act  as  filters,  permitting  only  the 
passage  of  air. 

Neumann  ("Ueberden  Keimgehalt  der  Luft  im  stadt.  Kranken- 
hause  Moabit,"  Vierteljahresschrift  f.  gerichtliehe  Medicin,  B.  xlv. 
p.  310,  1886)  made  35  experiments  after  Hesse's  method  to  deter- 
mine the  number  of  germs  which  exist  in  a  certain  volume  of 
atmospheric  air.  The  cultures  were  made  upon  meat  infusion- 
peptone -gelatine.  With  an  apparatus  of  special  construction,  from 
5  to  20  litres  of  air  were  taken  from  one  of  the  rooms  in  the 
Moabit  Hospital.  The  examination  of  air,  taken  at  different  ele- 
vations, from  1.40  to  3.20  m.,  showed  that  it  contained  about  the 
same  number  of  microbes.  In  the  morning  after  the  rooms  had 
been  swept,  from  80  to  140  microbes  were  found  in  every  10  litres 
of  air.  Four  consecutive  examinations  of  the  same  quantity  of 
air  taken  at  the  same  height  showed  a  gradual  decrease  in  the 
number  of  germs,  so  that  at  the  last  examination,  at  eight  o'clock 
in  the  evening,  only  from  4  to  10  germs  were  found.  Cocci  were 
more  abundant  than  bacilli,  and  microbes  were  more  frequently 
met  with  than  spores,  a  fact  which  had  already  been  established  by 
Hesse. 

Buchner  (Munch,  med.  Wochenschrift,  1888,  Nos.  15-17)  has 
recently  made  some  interesting  experiments  on  the  inhalation  of 
microbes  with  the  inspired  air,  and  has  come  to  conclusions  some- 
what different  from  those  heretofore  held.  The  animals  were 
exposed  to  a  spray  of  diluted  cultures  of  different  bacteria,  in  such 
a  way  that  only  the  finest  mist  of  the  spray  reached  them.  Control 
experiments  were  made  by  feeding,  so  as  to  exclude  accidental 
infection  through  the  alimentary  canal  by  swallowed  spray.  The 
results  showed  that  this  happened  very  seldom,  and  also  that  the 
amount  necessary  to  cause  infection  through  the  intestinal  canal  is 


SO UKCES    OF    INFECTION.  33 

much  larger  than  that  for  the  lungs.  The  bacteria  used  were 
those  of  anthrax,  with  their  spores,  and  those  of  chicken  cholera 
and  septicaBmia.  Irritation  of  the  bronchial  mucous  membrane 
retarded  the  ingress  of  microbes  into  the  circulation.  When  large 
quantities  of  bacilli  were  used  the  irritation  was  often  so  great 
that  a  hemorrhagic  pneumonia  resulted.  The  best  results  were 
obtained  by  using  only  the  spores,  after  destroying  the  bacilli  by 
drying.  The  growth  of  bacilli  was  very  rapid,  and  in  a  short 
time  the  microbe  could  be  found  in  the  pulmonary  capillaries. 
The  rapidity  with  which  the  microbes  entered  the  pulmonary 
tissue  was  proof  positive  that  a  more  direct  tolerance  was  effected 
than  through  the  lymphatics.  The  author  is  of  the  opinion  that 
the  chemical  irritation  exerted  on  the  walls  of  the  capillaries 
causes  the  formation  of  stomata,  through  which  the  bacilli  grow. 
These  experiments  demonstrate  also,  that  the  blood  microbes  are 
best  adapted  to  pass  through  the  pulmonary  tissues  into  the  circu- 
lation. The  microbes  of  anthrax,  recurrent  fever,  and  malaria  are 
the  most  striking  examples  of  the  blood  parasites  so  far  known. 
In  infection  caused  by  blood  microbes,  the  point  of  entrance  can- 
not always  be  found,  as  they  may  enter  through  apparently  intact 
surfaces.  Even  in  the  case  of  microbes  not  strictly  blood  micro- 
organisms, it  is  possible  for  them  to  penetrate  the  pulmonary  capil- 
laries and  be  transported  to  that  part  of  the  body  where  they 
afterward  initiate  morbid  conditions.  These  experiments  show 
conclusively  that  pathogenic  microbes  suspended  in  the  atmospheric 
air  can  enter  the  organism  through  the  respiratory  organs. 

Petri  ("  Zusammenfasseuder  Bericht  iiber  Nachweis  und  Bestim- 
intmg  der  pflanzlichen  Microorganismen  in  der  Luft,"  Centralblatt 
f.  Bacteriologie  u.  Parasitenkunde,  B.  ii.  Hefte  5  u.  6)  claims  that 
the  methods  so  far  employed  in  the  detection  of  pathogenic  germs 
in  the  air  have  not  succeeded  in  demonstrating  more  than  the 
microbes  of  pus,  a  circumstance  which  may  be  ascribed  to  the 
methods  employed,  as  some  pathogenic  germs  do  not  grow  upon 
gelatin  at  ordinary  room  temperature,  and  that  the  culture  of  the 
microbe  sought  for  may  become  obscured  by  cultures  of  other 
microbes. 

Emmerich  ("  Ueber  den  Nachweis  von  Erysipelkokken  in  einem 
Secirsaale,"  Deutsche  m,ed.  Wochenschrift,  1877,  No.  3)  by  means  ot 
an  aspiration  apparatus  obtained  air  from  an  old  dissecting-room, 
which  for  a  long  time  had  not  contained  any  erysipelatous  material, 
and  cultivated  from  it  the  cocci  of  erysipelas,  which  on  being  inocu- 
lated into  animals  produced  typical  erysipelas.  The  cocci  were  also 
found  in  shavings  of  the  floor  and  in  the  plastering  of  the  walls 
and  ceilings. 

Eiselsberg  ("  Nachweis  von  Erysipelkokken  in  der  Luft  chirur- 

3 


34  SOURCES    OF    INFECTION. 

gischer  Krankenzimmer,"  Langenbeck's  Archiv,  B.  xxxv.  Heft  1) 
made  a  series  of  experiments  for  the  purpose  of  ascertaining  the 
presence  of  pathogenic  microorganisms  in  the  air  of  hospital  wards 
occupied  by  surgical  patients.  By  exposing  for  a  certain  length  of 
time  glass  plates  coated  with  sterilized  gelatine  or  agar-agar  in  a 
room  occupied  by  four  cases  of  erysipelas,  twice  colonies  of  cocci 
were  found,  which,  however,  grew  only  to  a  limited  extent.  Inocu- 
lation upon  agar-agar  and  gelatine  as  well  as  upon  solid  blood- 
serum  showed  that  the  new  growth  was  composed  of  Fehleisen's 
streptococcus.  Its  identity  with  the  microbe  of  erysipelas  was 
further  demonstrated  by  inoculation  experiments  which  proved 
successful.  In  another  room  containing  surgical  patients,  where  all 
the  wounds  were  aseptic,  a  growth  of  the  staphylococcus  pyogenes 
aureus  developed  upon  culture  plates.  From  erysipelatous  patients 
during  the  stage  of  desquamatiou,  he  inoculated  sterilized  gelatin 
with  epidermic  scales,  and  in  four  out  of  five  cases  the  specific 
microbe  of  erysipelas  was  cultivated. 

At  the  last  Congress  of  Italian  Surgeons,  Durante  reported 
experiments,  performed  at  his  suggestion,  by  his  assistant,  to  deter- 
mine the  presence  of  germs  in  the  air  about  the  bed  of  a  surgical 
patient,  and  in  a  ward.  It  was  found  that  the  greatest  number  of 
germs  were  present  about  forty  inches  above  the  border  of  the  bed  ; 
in  all  other  directions  the  number  of  germs  greatly  decreased. 
Culture  materials  placed  beneath  the  bed,  and  about  the  bottoms  of 
the  neighboring  walls,  remained  frequently  sterile.  The  germs 
most  frequently  found  were  staphylococcus  pyogenes  aureus,  strep- 
tococcus of  erysipelas,  and  FrankePs  pneumococcus.  (Deutsche  meet. 
Wochenschrift,  May  3,  1888.) 

Wehde  investigated  the  in  factiousness  of  air  in  rooms  occupied 
by  phthisical  patients  by  exposing  plates  smeared  with  glycerin, 
and  with  the  dust  thus  collected  he  inoculated  guinea-pigs ;  the 
results  were  negative.  From  these  experiments  he  concluded  that 
the  air  expired  by  tubercular  persons  does  not  contain  the  bacillus, 
and  that  tubercular  sputum,  as  long  as  it  remains  moist,  does  not 
emit  microbes.  Similar  results  have  been  obtained  by  Celli  and 
Guaruieri,  Sirena,  Pern  ice,  and  Nicolas.  On  the  other  hand, 
Theodore  Williams  (Lancet,  1883),  by  resorting  to  the  same 
method,  and  exposing  the  plates  to  the  current  of  air  in  one  of  the 
ventilating  shafts  in  the  Brompton  Hospital  for  five  days,  demon- 
strated the  presence  of  tubercle  bacilli  upon  the  glycerin  plates. 
The  most  recent  and  reliable  experiments  on  the  existence  of  tuber- 
cle bacilli  in  hospitals  and  sick-rooms  have  been  made  by  Cornet, 
in  Koch's  Hygienic  Institute,  his  method  consisting  in  wiping  the 
Avails  of  wards  and  sick-rooms  at  places  where  the  dust  had  been 
left  undisturbed  for  a  long  time,  with  a  sterilized  sponge,  and 


SOUECES J3F    INFECTION.  35 

squeezing  it  out  in  bouillon,  so  as  to  liberate  any  germs  that  might 
have  been  caught.  This  fluid  was  then  injected  into  the  peritoneal 
cavity  of  guinea-pigs.  If  tubercle  bacilli  were  present,  the  animal 
invariably  manifested  symptoms  of  peritoneal  tuberculosis  three  to 
four  weeks  after  inoculation.  In  7  hospitals  in  Berlin,  21  wards 
occupied  by  tubercular  patients  were  examined.  The  sponge  was 
only  used  on  surfaces  which  had  never  been  exposed  to  direct  con- 
tact with  the  expectorations  of  the  patients.  In  15  out  of  the  21 
wards  tubercle  bacilli  were  present,  and  of  94  animals  which  were 
inoculated,  20  died  of  tuberculosis.  In  the  homes  of  fifty -three 
private  patients,  the  presence  of  tubercle  bacilli  was  demonstrated 
by  the  same  method  in  20. 

That  microbes  in  a  dried  state,  adherent  perhaps  to  particles  of 
dust,  follow  the  currents  of  atmospheric  air,  has  been  demonstrated 
by  the  history  of  endemics  of  malaria. 

Cadene  and  Malet  ("  Etude  experimental  de  la  transmission  de 
la  mave  par  contagion  mediate  ou  par  infection,"  Revue  de  MSdicale, 
t.  viii.  p.  227)  have  studied  experimentally  the  transmission  of  the 
bacilli  of  glanders  through  the  atmospheric  air,  and  have  come  to 
the  positive  conclusion  that  the  disease  is  not  contracted  in  this 
manner.  They  exposed  animals  which  are  known  to  be  very  sus- 
ceptible to  the  disease,  such  as  the  ass,  to  the  expired  air  of  animals 
suffering  from  glanders,  but  the  results  were  always  negative. 
They  next  produced  a  bronchitis  in  animals  by  inhalations  of 
bromine  before  they  were  exposed  to  the  expired  air  of  animals 
suffering  from  glanders,  but  the  results  remained  the  same.  The 
expired  air  of  diseased  animals  was  next  mixed  with  steam,  and 
the  latter  was  condensed,  but  no  bacilli  could  be  found,  and  inocu- 
lation in  guinea-pigs  only  yielded  negative  results.  The  same 
negative  results  were  obtained  by  passing  the  expired  air  over 
water,  as  the  latter  was  always  found  sterile.  The  air  in  the 
stables  occupied  by  the  diseased  animals  was  also  found  free  from 
bacilli.  Pure  cultures  of  the  bacilli  were  injected  into  the  trachea 
of  a  number  of  animals,  with  the  result  that  in  only  two  was  the 
disease  produced,  while  all  animals  inoculated  in  the  same  manner 
which  were  suffering  from  bromine  bronchitis  contracted  the  disease 
and  died. 

It  is  also  well  known  that  microbes  which  have  been  carried 
upward  by  currents  of  air  descend  by  virtue  of  their  own  weight. 
When  the  air  is  in  a  quiescent  state  the  lower  strata  contain 
microbes  in  greater  abundance  than  the  upper.  Klebs  found  that 
in  the  Campagna  districts,  near  Kome,  an  elevation  of  three  metres 
afforded  perfect  immunity  against  malaria.  Soyka  made  some 
observations  on  currents  of  air  as  a  vehicle  for  the  diffusion  of 
microbes  in  Klebs's  laboratory  at  Prague.  He  came  to  the  conclu- 


36  SOURCES    OF    INFECTION. 

sioii  that  very  slight  currents  convey  microbes  from  the  margins  of 
drying  fluids,  while  Naegeli  asserted  that  a  current  of  considerable 
force  is  necessary  to  effect  such  transportation,  and  that  the  lifting 
up  of  the  particles  into  the  air  by  the  current  was  greatly  influenced 
by  the  force  of  adhesion  which  exists  between  the  particles  and 
the  surface  to  which  they  adhere. 

The  great  media  for  the  diffusion  of  pathogenic  microbes  over 
the  surface  of  the  globe  are  the  air  and  water.  Some  of  the  micro- 
organisms, as  the  pus-microbes,  appear  to  be  almost  omnipresent, 
while  others  are  diffused  over  a  more  limited  area,  their  existence 
being  dependent  upon  certain  conditions  of  the  soil  or  temperature. 
Water  as  a  medium  of  diffusion  and  vehicle  for  the  entrance  into 
the  organism  of  pathogenic  microbes,  is  of  greater  interest  to  the 
physician  than  the  surgeon.  The  superficial  layer  of  the  soil  con- 
tains most  of  the  disease  germs  and  spores,  as  they  are  deposited 
upon  it  from  the  air,  and  carried  into  it  by  water  which  contains 
them,  the  soil  in  the  latter  instance  serving  the  purpose  of  a  filter- 
ing substance.  To  the  surgeon,  direct  infection  with  microbes  of 
the  soil  has  awakened  new  interest  by  Nicolaier's  discovery  that 
the  bacillus  of  tetanus  has  here  its  natural  habitat,  and  from  the 
well-known  circumstance  that  the  bacillus  of  anthrax  is  known  to 
multiply  in  the  soil  of  pastures  which  have  been  inhabited  by 
animals  suffering  from  this  disease. 


CHAPTER    IV. 

LOCALIZATION  OF  MICROORGANISMS. 

EVERY  surgeon  has  had  frequent  opportunities  to  observe  cases 
in  which  a  slight  subcutaneous  injury  was  followed  by  a  destructive 
inflammation,  an  inflammation  not  produced  by  the  trauma,  but  by 
the  localization  of  pathogenic  microbes  in  the  tissues  altered  by  the 
injury.  Thus  Chaveau  (Comptes  rendus,  t.  76,  p.  1092)  has  shown 
experimentally  that  subcutaneous  crushing  of  tissue  furnishes  a 
favorable  condition  for  the  localization  of  pathogenic  microorgan- 
isms carried  to  the  part  by  the  circulating  blood.  When  he  injected 
a  putrid  fluid  directly  into  the  circulation  of  young  rams  shortly 
before  subcutaneously  crushing  the  testicle,  the  injured  organ  always 
became  the  seat  of  septic  gangrene,  while  without  such  injection 
the  crushed  testicle  disappeared  by  uecrobiosis  and  absorption. 
Gangrene  only  occurred  if  the  putrid  fluid  contained  bacteria ;  it 
did  not  take  place  if  the  fluid  was  carefully  filtered.  Extensive 
subcutaneous  injuries,  as  severe  contusions,  rupture  of  tendons  or 
muscles,  and  crushing  of  bone,  are  not  followed  by  suppuration, 
unless  the  injured  tissues  become  subsequently  the  seat  of  infection 
with  pus-microbes.  A  patient  may  have  been  the  subject  of  tuber- 
cular infection  for  an  indefinite  period  of  time,  and  yet  may  present 
the  appearances  of  ordinary  health  until  some  slight  injury  deter- 
mines localization  of  the  bacillus  of  tuberculosis  in  the  part  injured, 
an  occurrence  which  is  followed  by  a  localized  tuberculosis  from 
which,  later,  regional  and  general  dissemination  takes  place,  to 
which  the  patient  finally  succumbs,  unless  the  tubercular  focus  is 
removed  by  an  early  operation.  These  facts  suggest  very  strongly 
that,  in  the  hypothetical  cases,  suppuration  and  tuberculosis  would 
not  have  taken  place  in  the  part  injured  without  the  injury,  and 
that  the  injury  certainly  would  not  have  produced  suppuration  or 
tuberculosis  unless  the  respective  patients  had  been  infected  pre- 
viously with  specific  pathogenic  microorganisms.  The  injury  in 
these  cases  creates  a  so-called  locus  minoris  resistentice,  which  may 
signify  one  of  two  things  :  1.  Diminution  or  suspension  of  resist- 
ance on  the  part  of  the  injured  tissues  to  the  action  of  pathogenic 
microorganisms,  which  was  present  in  the  part  at  the  time  of  injury  ; 
or,  2.  The  injury  so  alters  the  tissues  that  pathogenic  germs,  which 
were  present  in  the  circulation  without  having  given  rise  to  symp- 


38  LOCALIZATION    OF    MICRO-ORGANISMS. 

torns,  become  arrested,  and  find  at  the  same  time  the  necessary 
nutrient  medium  for  their  multiplication.  These  questions  have 
been  made  the  subject  of  patient  experimental  inquiry  by  a  number 
of  investigators,  the  most  important  results  of  which  will  now  be 
mentioned. 

1.  BACILLI  OF  ANTHRAX. — Huber  ("  Experimented  Unter- 
suchungen  liber  Localisation  von  Krankheitsstoffen,"  Virchow's 
Archiv,  B.  vi.,  1886)  calls  attention  to  the  circumstance  that  a 
number  of  infectious  diseases,  such  as  tubercular  affections  of  the 
bones  and  joints,  certain  cases  of  pya3mia,  osteomyelitis,  and  diffuse 
suppurative  inflammation  in  different  tissues,  are  liable  to  follow 
injuries  unattended  by  infection  from  without.  Again,  we  have 
local  infective  processes  which  occur  as  complications  during  the 
course  of  typhus  and  typhoid  fevers,  syphilis,  and  other  infective 
diseases.  Through  these  extraneous  influences,  or  accidental  con- 
ditions, certain  parts  of  the  body  are  rendered  more  susceptible  to 
the  development  of  serious  local  disturbances  under  the  action  of 
infective  germs  than  the  remainder  of  the  body ;  in  other  words,  a 
local  predisposition,  a  locus  minoris  resistentice,  is  created.  The 
experiments  of  the  author  were  made  on  rabbits,  in  which,  by  the 
application  of  croton  oil  to  the  ear,  he  produced  a  tissue  lesion  by 
the  inflammation  which  followed.  Only  one  ear  was  thus  treated, 
the  other  being  left  in  a  normal  condition  in  order  to  compare  the 
results  of  the  subsequent  action  of  pathogenic  microbes  upon  nor- 
mal and  inflamed  tissues.  The  virus  selected  was  a  pure  culture 
of  the  bacilli  of  anthrax,  and  the  reliability  of  the  culture  was 
always  tested  before  inoculations  were  made.  The  inoculation  was 
always  made  at  the  root  of  the  tail,  as  far  as  possible  from  the  seat 
of  inflammation  produced  by  the  croton  oil.  According  to  the 
stage  of  inflammation  in  which  the  action  of  the  bacilli  of  anthrax 
was  intended  to  be  studied,  the  croton  oil  was  applied  either  before 
or  after  the  inoculation.  Immediately  after  death  the  ears  were 
removed  and  carefully  preserved  for  subsequent  examination,  at 
the  same  time  serum  and  blood  were  separately  taken  in  sterilized 
glass-tubes  from  the  inflamed  ear  under  strict  antiseptic  precau- 
tions. For  microscopical  examination  the  specimens  were  carefully 
stained,  while  cultivations  were  made  by  inoculating  sterilized 
nutrient  fluids,  as  at  that  time  the  method  of  cultivation  on  solid 
nutrient  media  inaugurated  by  Koch  was  not  known.  These  ex- 
periments enabled  the  author  to  state  that  in  all  stages  of  the 
inflammatory  process  the  bacilli  were  never  found  outside  the  walls 
of  the  capillary  bloodvessels  in  the  tissue  placed  in  a  condition  of 
inflammation  by  the  croton  oil.  Their  number  within  the  blood- 
vessels depended  upon  the  conditions  of  the  inflamed  bloodvessels. 
During  the  first  stage  of  inflammation,  marked  by  oedema  without 


BACILLI    OF    ANTHRAX.  39 

suppuration,  more  bacilli  were  found  within  the  inflamed  vessels 
than  in  the  corresponding  vessels  of  the  opposite  ear.  The  bacilli 
were  found  equally  distributed  in  the  arteries,  veins,  and  capilla- 
ries, but  were  never  found  anywhere  in  the  para-vascular  tissues. 
The  first  stage  of  inflammation  lasted  on  an  average  seven  hours 
and  a  half,  after  which  suppuration  initiated  the  second  stage. 
During  this  stage,  the  bacilli  disappeared  within  the  bloodvessels ; 
this  could  be  more  readily  seen  forty-eight  hours  after  the  croton 
oil  was  applied.  During  the  third  stage,  when  granulations  com- 
menced to  form,  a  complete  change  was  again  observed  in  the 
bacteriological  condition  of  the  inflamed  part.  The  height  of  this 
stage  is  reached  on  the  tenth  day.  During  this  stage  the  bacilli 
reappear  in  the  inflamed  tissue,  where  they  can  be  seen  in  consid- 
erable number,  especially  in  the  interior  of  new  capillary  blood- 
vessels. During  the  process  of  cicatrization  the  number  of  bacilli 
in  a  corresponding  area  of  both  ears  was  about  the  same.  From 
these  observations  Huber  concluded  that  the  bacillus  of  anthrax 
finds,  in  a  soil  prepared  by  inflammation  induced  with  croton  oil, 
a  locus  minori*  resistentice,  which  presents  more  favorable  condi- 
tions for  its  growth  than  tissues  in  other  parts  of  the  body.  Sup- 
puration appeared  to  neutralize  the  anthracic  process  by  the 
destructive  effect  of  the  pus  ptomaines  upon  the  bacilli.  The  con- 
clusions which  he  has  drawn  from  his  experiment  may  be  sum- 
marized as  follows :  Localization  of  preexisting  microorganisms  in 
tissues  prepared  by  injury  or  disease  takes  place,  provided  that  the 
necessary  conditions  for  their  growth  are  present. 

In  looking  over  different  pathological  conditions  we  frequently 
meet  with  a  so-called  locus  minoris  resistentice ;  at  any  rate,  if  we 
search  only  for  that  which  should  mean  what  has  been  described 
above,  it  is  not  difficult  to  conceive  how  slight  injuries,  wounds, 
contusions,  etc.,  should  in  this  manner  give  rise  to  serious  affec- 
tions. But  not  only  do  direct  tissue  lesions,  as  hemorrhages, 
necrosis,  hypersemia,  fractures,  etc.,  act  in  this  manner,  but  a 
variety  of  pathological  conditions  of  a  general  nature  may  serve 
the  same  purpose  as  imperfect  digestion,  enfeebled  circulation  and 
respiration,  and  exposure  to  cold.  All  these  ill-defined  conditions 
belong  here,  and  through  their  instrumentalities  the  localization  of 
infective  germs  is  favored.  In  mixed  infections  it  can  be  said  that 
certain  infective  microbes  prepare  the  tissues  for  the  reception  and 
growth  of  other  pathogenic  germs. 

Muskatbliith  (u  Neue  Versuche  iiber  Infection  von  den  Lungen 
aus,"  Centmlblatt  /.  fiacteriologie  u.  Parasitenkunde,  B.  1 ,  No.  2) 
has  made  some  very  interesting  and  practical  experiments  on  in- 
fection through  the  respiratory  passages.  The  bacillus  of  anthrax 
was  used.  The  infection  was  made  in  two  ways  :  1.  Direct  injec- 


40  LOCALIZATION    OF    MICRO-OKG  ANISMS . 

tion  of  a  pure  culture  into  the  trachea.  2.  Injection  through  a 
tracheal  tube.  In  the  latter  case  the  injection  was  not  made  until 
the  tracheal  wound  had  completely  healed  around  the  canula,  and 
the  tube  was  left  in  situ  until  the  death  of  the  animal.  The  tra- 
cheal wound  in  these  cases  never  became  infected.  Direct  injections 
into  the  trachea  always  produced  positive  results,  the  animals 
dying  of  anthrax  in  from  forty  to  forty-eight  hours.  As  in  these 
instances  the  tracheal  wound  always  became  infected,  it  became 
necessary  to  kill  the  animals  soon  after  the  injection  in  order  to 
determine  the  effect  of  the  bacilli  on  the  pulmonary  tissues.  On 
microscopical  examination  of  the  specimens  of  animals  killed 
sixteen  hours  after  direct  injection,  free  bacilli  were  found  in  the 
wound,  the  walls  of  the  alveoli,  in  the  juice  canals  and  only 
a  few  rods  in  the  interior  of  the  alveoli  themselves  and  the 
lumen  of  the  bronchial  tubes.  The  bacilli  were  most  abundant 
in  the  so-called  dust  cells,  derivatives  of  the  alveolar  epithelia. 
No  bacilli  could  be  seen  in  the  peri-bronchial  and  peri-vascular 
lymph  spaces.  On  examination  of  the  bronchial  glands,  a  very 
peculiar  arrangement  of  the  bacilli  was  found.  Each  section  con- 
tained countless  bacilli  which  occupied  almost  exclusively  the 
lymph  channels  of  these  organs ;  in  the  bloodvessels  they  were 
scanty.  The  bacilli  and  threads  surrounded  the  periphery  of  the 
cortical  follicles  in  the  shape  of  a  very  dense  zone,  the  density  of 
which  diminished  toward  the  centre  of  the  follicle  and  followed 
the  medullary  strings.  In  animals  killed  seventeen  hours  after 
direct  injection,  small  pieces  of  the  lung  or  liver  planted  on  a 
proper  culture-soil  were  soon  surrounded  by  a  copious  growth  of 
bacilli.  In  animals  injected  through  a  canula  after  complete  cica- 
trization of  the  tracheotomy  wound,  killed  after  forty  hours,  the 
bacilli  were  found  most  numerous  in  the  pulmonary  bloodvessels, 
while  the  dust  cells  contained  only  a  single  rod,  if  any.  Most  all 
of  the  bacilli  had  left  the  lymphatic  glands,  and  had  passed  into 
the  general  circulation.  From  these  experiments  the  author  con- 
cluded that  the  bacilli  of  anthrax  can  enter  the  circulation  through 
the  mucous  membrane  of  the  bronchial  tubes,  and  that  the  juice 
canals,  lymphatic  channels  of  the  bronchial  tubes,  lungs,  and  the 
bronchial  glands  are  the  channels  through  which  infection  takes 
place.  The  carriers,  which  are  directly  concerned  in  the  transpor- 
tation of  the  bacilli  from  the  mucous  surface  into  the  lymphatic 
system,  are  yet  to  be  discovered.  It  seemed  strange  to  the  author 
that  no  bacilli  could  be  found  in  leucocytes,  but  always  only  in 
epithelial  cells.  Final  localization  of  the  bacilli  of  anthrax 
which  have  entered  the  circulation  through  the  lungs  takes  place 
in  distant  organs  through  the  medium  of  the  general  circulation 
by  implantation  upon  the  endothelial  lining  of  the  capillary  ves- 


PLATE    I. 


v^ 


Parasitic  interstitial  pneumonia,  from  the  lungs  of  a  guinea-pig 
infected  with  anthrax.  Hartnach.  Obj.  4.  O.  2.  Picro-carmine- 
gentian. 

a.  Periarterial  growth. 

b.  Wall  of  artery. 

c.  Thrombus  with  bacilli. 


BACILLI    OF    TUBERCULOSIS.  41 

sels.  Other  experimenters  affirm  that  if  the  bacilli  of  anthrax  are 
injected  in  moderate  quantities  into  the  circulation  of  animals,  they 
disappear  soon  from  the  blood  without  having  produced  any 
pathogenic  eifects ;  but,  if  in  animals  thus  injected  a  contusion  is 
produced  in  some  part  of  the  body,  the  bacilli  pass  out  of  the 
vessels  into  the  connective  tissue  along  with  the  blood,  grow  there, 
and  soon  cause  the  formation  of  the  characteristic  inflammatory 
product,  the  diffusion  of  the  disease,  and  its  fatal  termination. 

2.  BACILLI  OF  TUBERCULOSIS. — Yolkmann  ("  Chirurgische 
Erfahrungen  liber  die  Tuberculose,"  Verh.  der  Deutschen  G-esell- 
scha/t  /.  Chirurgie,  1885),  from  an  extensive  clinical  experience, 
came  to  the  conclusion  a  long  time  ago  that  a  severe  trauma  seldom, 
if  ever,  gives  rise  to  tuberculosis  at  the  seat  of  injury,  but  that 
where  local  tuberculosis  is  caused  by  an  injury  the  trauma  was 
always  slight,  sometimes  almost  insignificant.  He  maintains  that 
the  active  tissue-changes  which  follow  a  severe  injury  during  the 
reparative  process  counteract  the  growth  and  propagation  of  the 
bacillus.  Luecke  attributes  to  exposure  to  cold  an  important  role 
in  the  causation  of  tubercular  and  other  infective  forms  of  inflam- 
mation, as  he  asserts  that  the  sudden  diminution  of  blood-supply 
to  the  cutaneous  surface  causes  internal  congestions  which  favor  the 
localization  of  pathogenic  germs  in  some  one  of  the  congested  parts, 
otherwise  predisposed  to  the  specific  inflammation. 

Schueller  (Experimentette  und  histologische  Untersuchungen  uber 
Entstehung  der  skrophulosen  u.  tuberJculosen  Grelenkleiden,  Stuttgart, 
1880)  studied  the  localization  of  the  tubercular  virus  experiment- 
ally in  the  same  manner  as  others  have  studied  the  localization  of 
pus-microbes.  He  inoculated  animals  with  the  products  of  tuber- 
cular inflammation,  subsequently  produced  contusions  and  sprains 
of  joints,  and  observed  that  localization  usually  occurred  at  the 
seat  of  injury.  If  the  tubercular  virus  was  introduced  by  inhala- 
tion, the  same  typical  lesions  occurred  in  the  injured  joints  as  when 
infection  was  made  more  directly.  In  all  cases  the  products  of  the 
local  lesion  corresponded  with  the  character  of  the  material  intro- 
duced through  some  remote  point.  Surgeons  are  well  aware  of  the 
danger  of  general  infection  following  an  injury  to  a  part  or  an 
organ  the  seat  of  a  local  tuberculosis,  more  particularly  in  cases  of 
tubercular  disease  of  joints.  Cases  like  the  following  are  not  of 
rare  occurrence. 

Szuman  ("  Brisement  force  eines  skrefulos  entzundeten  Knie- 
gelenkes  und  konsecutiver  acuter  allgemeiner  Miliar-tuberculose," 
Centralblatt  f.  Chirurgie,  1885,  No.  29)  relates  the  case  of  a  small, 
well-nourished  child,  the  subject  of  tuberculosis  of  one  of  the  knee- 
joints.  The  joint  was  punctured  with  a  fine  trocar,  and  although 
no  pus  escaped,  it  was  washed  out  through  the  cauula  with  a  solu- 


42  LOCALIZATION    OF    MICRO -O EGA N ISMS. 

tion  of  carbolic  acid.  The  swelling  diminished,  but  the  joint 
became  fixed  by  false  ankylosis  at  nearly  a  right  angle.  Rest  in 
bed  and  extension  with  weight  and  pulley  had  no  effect.  Under 
an  anaesthetic  brisement  force  was  made,  and  a  plaster-of-Paris 
bandage  applied.  The  operation  was  followed  by  a  continued 
fever,  the  temperature  at  times  reaching  40°  C.  (104°  F.),  rapid 
emaciation,  cough,  expectoration,  and  rales  over  both  lungs,  puru- 
lent otitis  media,  and  death  in  a  few  weeks.  The  necropsy 
revealed  acute  miliary  tuberculosis  of  lungs  and  several  other 
organs.  The  joint  was  the  seat  of  a  caseous  osteo-tuberculosis. 

Verchere  ("  Coxalgie  ancienne,  Redressement  et  immobilisation 
dans  un  bonne  position,  Meuingite  tuberculeux,  Tuberculose 
miliare  generalissee,  Mort,"  Progrls  Med.,  1886,  No.  24).  In  a 
boy  sixteen  years  old,  who  had  suffered  for  one  and  three-quarters 
of  a  year  from  coxitis,  reduction  of  a  semiflexed  leg  was  made 
under  ether.  But  little  force  was  used,  and  the  limb  was  immo- 
bilized. Patient  was  emaciated,  but  otherwise  in  fair  health. 
The  next  morning  the  temperature  was  40°  C.  (104°  F.),  and 
symptoms  of  meningitis  were  present.  These  subsided  after  ten 
days,  but  a  moderate  fever  persisted  with  gradual  decline  of  health. 
After  two  months,  pulmonary  signs  could  be  detected ;  four  weeks 
afterward,  death.  Post-mortem  showed  general  tuberculosis  and 
tubercular  meningitis.  The  author  attributes  the  general  dissemi- 
nation to  the  redressement. 

In  these  cases,  as  in  so  many  others  of  a  similar  character  which 
have  been  reported  by  different  surgeons,  the  violence  used  in 
straightening  the  limb  caused  laceration  of  some  of  the  small  ves- 
sels in  the  tubercular  focus,  which  opened  a  direct  road  for  the 
bacilli  into  the  circulation,  which  by  their  rapid  diffusion  through 
the  systemic  circulation,  caused  acute  miliary  tuberculosis.  Im- 
perfect operations  for  local  tuberculosis  have  been  followed  by  the 
same  disastrous  consequences.  The  veins,  in  the  indurated  tissues 
within  and  around  the  tubercular  product,  when  opened  by  the 
knife,  scissors,  or  a  sharp  spoon,  do  not  contract,  and  cells  contain- 
ing the  bacilli,  as  well  as  free  bacilli,  find  ready  access  into  the  open 
vessels,  and  after  they  have  entered  the  circulation  miliary  tubercu- 
losis is  produced  by  their  localization  in  distant  organs.  In  opera- 
tion wounds,  after  incomplete  removal  of  a  tubercular  focus,  it  is, 
therefore,  advisable  to  prevent  the  traumatic  diffusion  of  the  bacilli 
by  searing  their  surface  with  the  actual  cautery,  which  not  only 
prevents  the  entrance  of  bacilli  into  the  circulation,  but,  at  the  same 
time,  adds  to  the  prospects  of  a  permanent  result  by  destroying 
infected  tissues. 

Wartmann  (u  Die  Bedeutung  der  Resection  tuberculos  erkrank- 
ter  Gelenke  fiir  die  Generalisation  der  Tuberculose,"  Gentmlblatt  f. 


PUS-MICKOBES.  43 

Chirurgie,  1887  No.  2),  has  collected  74  excisions  of  tuberculous 
joints  made  at  the  Canton  Spital  in  St.  Gall,  for  the  purpose  of 
ascertaining  the  immediate  effects  of  the  operation  in  causing  gene- 
ralization of  the  tuberculosis.  Of  this  number,  11  died,  and  in  2 
of  them  death  was  caused  by  miliary  tuberculosis  soon  after  the 
operation,  the  disease  being  produced  by  inoculation  from  the 
wound  surfaces.  He  next  collected  837  resections  from  other 
sources,  with  225  deaths ;  of  these,  26  cases  of  acute  miliary  tuber- 
culosis could  be  traced  to  inoculation  during  the  operation. 

3.  PUS-MICROBES. — When  by  mechanical,  chemical,  or  other 
injury,  the  vitality  of  tissue  cells  is  lowered,  a  door  is  opened  for 
the  admission  of  such  organisms  which,  having  once  penetrated  the 
tissues  or  the  blood,  find  a  suitable  soil  for  multiplication,  and  these 
may  prove,  by  their  mere  numbers,  or  by  their  effects,  injurious  or 
fatal  to  the  whole  body.  Nothing  can  demonstrate  this  better  than 
the  experiments  recently  made  by  Orth  and  Wyssokowitsch,  who 
found  that  staphylococci  could  be  injected  into  the  blood  of  a 
rabbit  without  apparent  injury  to  it,  but  if  before  the  injection  a 
slight  mechanical  injury  was  inflicted  on  the  valve  of  the  heart, 
typical  endocarditis  was  at  once  produced. 

To  Rosenbach  ("  Bemerkungen  zur  Lehre  von  der  Endocarditis, 
mit  besonderer  Berucksichtigung  der  experimentellen  Ergebnisse," 
Deutsche  med.  Wochenschrift,  B.  xiii.  Nos.  32-33,  1887)  belongs  the 
credit  of  having  first  studied  the  influence  of  trauma  in  the  locali- 
zation of  microbes  upon  the  valves  of  the  heart  in  cases  of  artifi- 
cially-produced ulcerative  endocarditis.  He  found  in  his  experi- 
ments and  in  post-mortem  examination  in  cases  of  ulcerative 
endocarditis,  microbic  emboli  in  the  valves  and  in  the  infarcts  of 
other  organs,  and  classifies  this  affection  with  pya3mia.  The  more 
frequent  occurrence  of  endocarditis  in  the  left  side  of  the  heart,  he 
explains  by  assuming  that  the  microbe  finds  a  better  soil  in  the 
arterial  blood,  as  when  the  affection  occurs  in  the  foetus  during 
iutra-uterine  life,  when  the  blood  in  both  sides  of  the  heart  is  of 
about  the  same  composition,  the  valves  on  both  are  affected  with 
the  same  frequency. 

Wyssokowitsch  ("  Beitrage  zur  Lehre  von  der  Endocarditis." 
Virchow's  Archiv,  B.  ciii.  Heft  6)  has  determined  with  great 
accuracy  the  influence  of  traumatism  in  causing  localization  of 
pathogenic  germs,  and  has  found  that,  by  introducing  a  rod  into 
the  jugular  vein,  he  was  able  to  cause  laceration  of  the  valves, 
and  that  then,  on  subsequent  injection  of  a  culture  of  staphylo- 
cocci into  the  blood,  ulcerative  endocarditis  developed  at  the  seat 
of  injury.  The  effects  of  the  traumatic  lesion  in  this  instance  are 
no  doubt  chiefly  due  to  the  production  of  a  locus  minoris  resistentice 
in  the  endothelial  and  connective-tissue  cells,  as  the  result  of  the 


44  LOCALIZATION    OF    MICRO-ORGANISMS. 

incipient  inflammation  induced  by  it.  Similar  results  were  ob- 
tained by  Frankel  and  Siinger  ("  Untersuchungen  liber  die  Aetio- 
logie  der  Endocarditis/7  Centralblatt  f.  klinische  Medicin,  1886,  p. 
577). 

Rinne  ("  Der  Eiterungsprocess  und  seine  Metastaseu,"  Archiv  /. 
kiln.  Chirurgie,  B.  39,  p.  19)  injected  pure  cultures  of  the  different 
kinds  of  pus-microbes  directly  into  the  circulation  in  animals,  and 
found  that,  as  a  rule,  no  harm  resulted.  In  rabbits  he  injected 
from  two  to  three  Pravaz's  syriugefuls  of  uufiltered  and  filtered 
suspension  of  pure  cultures  in  distilled  water,  and  after  repeating 
the  injections  several  times  inflicted  all  kinds  of  subcutaneous 
lesions  without  causing  serious  disturbances.  Only  in  a  few  in- 
stances were  pysemic  metastases  observed,  and  this  occurred  usually 
only  in  cases  where  undiluted  gelatin  cultures  were  used.  In 
several  dogs  he  made  subcutaneous  fractures  and  then  injected  fluid 
cultures  of  pus-microbes  in  large  doses  into  the  peritoneal  cavity, 
but  no  suppuration  occurred  at  the  seat  of  injury.  In  six  rabbits 
he  fractured  the  femur  subcutaueously,  and  then  injected  pure  cul- 
tures into  the  jugular  or  one  of  the  auricular  veins,  but  in  only 
one  of  them  did  the  seat  of  fracture  suppurate,  and  in  this  case  no 
other  metastases  were  discovered.  In  two  experiments  where  he 
injected  osteomyelitic  pus  diluted  with  distilled  water  suppuration 
was  produced  at  the  seat  of  fracture  and  at  the  same  time  abscesses 
were  found  in  the  heart-muscle  and  the  kidneys  at  the  autopsy. 

Roseubach  ("Beitriige  zur  Kenntniss  der  Osteomyelitis/'  Deutsche 
Zeitschrift  /  Cliirurgi'e,  1878,  p.  369)  ascertained  that  acute  sup- 
purative  osteomyelitis  in  animals  could  only  be  produced  experi- 
mentally by  injecting  pus  directly  into  the  circulation  and  by 
injuring  the  medullary  tissue  a  few  days  before,  or  after,  the  inocu- 
lation. Kocher  ("  Die  acute  Osteomyelitis  mit  besouderer  Riick- 
sicht  auf  ihre  Ursachen,"  Deutsche  Zeitschrift/.  Chirurgie,  1879,  p. 
87),  Becker  ("  Ueber  die  Osteomyelitis  erzeugeudeu  Mikroorgan- 
ismen,"  Deutsche  med.  Wochenschrift,  1883,  No.  46),  and  Krause 
("  Ueber  einen  bei  der  acuten  infectiosen  Osteomyelitis  beim 
Menschen  vorkommenden  Micrococcus,"  Fortschritt.  der  Medicin, 
1884,  B.  ii.  No.  7)  repeated  the  experiments  of  Rosenbach  and 
came  essentially  to  the  same  conclusions.  Both  Kocher  and  Rosen- 
bach  look  upon  the  altered  circulation  in  the  injured  tissues  as  the 
condition  which  determined  localization,  while  they  admit  that  the 
immediate  tissue  lesions,  hemorrhage  and  necrosis,  might  have  the 
same  effect.  Upon  the  same  hypothesis  Kocher  ("  Zur  Pathologic 
u.  Therapie  des  Kropfes,"  Deutsche  Zeitschrift  f.  Chirurgie,  1878,  B. 
x.  p.  189)  explained  the  occurrence  of  traumatic  suppurative  stru- 
mitis  in  a  hyperplastic  struma. 

Ribbert  ("  Die  Schicksale  der  Osteomyelitiskokken  im  Orgauis- 


PUS-MICROBES.  45 

mus,"  Berl.  klin.  Woch.,  1884,  No.  51)  used  in  his  experiments  an 
emulsion  of  a  pure  culture  of  osteomyelitis  cocci  which  was  injected 
directly  into  the  circulation.  A  few  days  after  the  injection  the 
microbes  had  disappeared  al mostly  completely  from  the  circulation. 
At  this  stage  they  could  only  be  found  within  the  interior  of  the 
white  blood -corpuscles  and  never  free  in  the  plasma  of  the  blood. 
After  twenty-four  hours  they  could  be  detected  in  almost  every 
organ  of  the  body.  In  the  liver  they  were  most  abundant,  but, 
almost  without  exception,  only  in  the  interior  of  white  blood-cor- 
puscles. In  the  lungs  they  were  often  so  numerous  as  to  obstruct 
completely  some  of  the  capillary  vessels ;  when  less  abundant  they 
were  in  the  interior  of  white  blood- corpuscles  which  were  aggre- 
gated in  groups.  In  the  spleen  and  lymphatic  glands  they  were 
not  numerous,  but  in  the  kidneys  they  were  again  more  abundant, 
especially  in  the  glomeruli,  and  also  in  some  of  the  loops  of  the 
tubuli  uriniferi.  Later,  they  disappeared  from  all  the  organs  with 
the  exception  of  the  kidneys.  In  all  probability  they  are  not 
destroyed  in  the  organism,  as  they  thrive  in  the  lungs  very  well,  as 
has  been  shown  by  injections  into  the  trachea,  but  they  are  con- 
veyed along  the  bloodvessels  to  some  excretory  organ.  In  the 
kidney  localization  takes  place  for  several  reasons.  Embolic 
obstruction  is  the  most  important  factor.  The  anatomical  structure 
of  the  bloodvessels  of  the  glomeruli  explains  their  arrest  in  this 
part  of  the  kidney,  as  in  the  lungs  and  liver,  on  account  of  a  more 
free  anastomosis  of  the  bloodvessels,  the  cocci  are  more  easily  dis- 
lodged. In  the  kidney,  the  growth  of  the  embolic  masses  in  the 
vessels  of  the  glomeruli  can  be  easily  followed  through  the  several 
stages.  "But  the  process  is  limited  to  a  few  places,  as  many  of  the 
masses  are  removed  by  the  circulation  in  the  same  manner  as  in  the 
liver  and  lungs.  Abscesses  in  different  parts  of  the  body  following 
injections  of  pus-microbes  into  the  circulation  are  produced  by 
embolism.  Suppuration  is  very  likely  to  take  place  in  the  connec- 
tive tissue,  as  here  the  circulation  is  comparatively  slow  and  conse- 
quently the  removal  of  cocci  attended  with  difficulties.  The 
microorganisms  of  osteomyelitis  are  eliminated  through  the  kidney 
the  same  as  the  microbes  of  other  infective  diseases,  and  conse- 
quently localization  is  very  likely  to  take  place  in  this  organ.  Six 
hours  after  injection  large  colonies  of  cocci  could  be  seen  in  the 
straight  and  convoluted  tubules.  Finally,  it  is  well  known  that  in 
the  living  body  localization  of  microbes  takes  place  in  the  tissues 
which  are  the  seat  of  a  trauma,  and  the  influence  of  this  exciting 
cause  has  been  abundantly  demonstrated  by  different  experimenters 
who  have  produced  acute  osteomyelitis  in  animals  infected  with  pus- 
microbes,  by  producing  fracture  of  a  bone  or  contusion  of  the  medul- 
lary tissue.  A  number  of  experiments  made,  among  others  by 


46  LOCALIZATION    OF    MICRO-ORGANISMS. 

Ribbert,  on  the  production  of  myo-  and  endo-carditis  in  rabbits, 
have  shown  that  abscesses  can  be  produced  in  other  organs  if  the 
pyogenic  microbes  are  attached  to  foreign  bodies  which  cannot  pass 
through  the  pulmonary  filtrum.  Thus  Ribbert  was  able  to  produce 
myocarditis  by  using  a  cultivation  of  staphylococcus  pyogenes 
auretis  on  potato,  if  he  took  the  precaution  in  removing  the  culture 
from  the  surface  of  the  potato  to  scrape  off  also  the  superficial  layer 
of  the  potato  itself.  The  particles  of  potato  in  these  experiments 
determined  suppuration  by  causing  localization  of  the  microbes,  as 
the  foreign  bodies  were  too  large  to  pass  through  the  capillary 
vessels  and  were  not  capable  of  removal  by  absorption. 

A  subcutaneous  fracture  occasionally  becomes  the  seat  of  an  acute 
osteomyelitis. 

Stein  thai  relates  two  such  cases  ("  Ueber  Vereiterung  subkutaner 
Fraktureu,"  Deutsche  med.  Wochenschrifi,  No.  21,  1887).  One  case 
occurred  in  a  man  twenty-eight  years  of  age,  who,  having  fallen 
from  a  tree,  sustained  a  fracture  of  the  neck  of  the  right  femur, 
also  of  the  trochanter  major,  and  a  Colles's  fracture  of  the  right 
forearm.  Suppuration  began  in  the  hip-joint  together  with  inflam- 
mation of  the  knee-joint.  In  spite  of  early  and  free  incisions  the 
patient  died,  thrombosis  of  the  left  femoral  vein,  and  atrophy  with 
nervous  disturbances  in  the  right  ulnar  region  being  present.  Post- 
mortem revealed  lobular  pneumonia  in  the  left  lower  lobe.  The 
second  case  was  that  of  a  woman  thirty-four  years  old  in  whom, 
under  chloroform  narcosis,  reduction  of  a  dislocation  of  the  left 
hip-joint  was  attempted.  During  the  manipulation  the  head  of  the 
femur  was  broken  off.  After  twelve  days  an  abscess  had  formed 
at  the  seat  of  fracture,  which  was  incised  and  drained.  The  patient 
recovered.  Steiuthal  believes  that  suppuration  in  these  cases  was 
the  result  of  localization  of  pus- microbes  in  the  tissues  necrosed  by 
the  injury. 

During  my  recent  visit  in  Zurich  (Four  Months  Among  the  Sur- 
geons of  Europe,  p.  128,  Chicago,  1887)  I  saw  a  very  interesting 
case  of  this  kind  in  Kronlein's  wards.  In  this  instance  infection 
probably  took  place  through  suppurating  wounds  distant  from  the 
fractures.  The  patient  was  a  young  man  who  had  sustained  several 
subcutaneous  fractures  from  a  fall,  and  at  the  same  time  a  lacerated 
wound  of  the  groin.  The  case .  progressed  favorably  until  the 
wound  commenced  to  suppurate,  when  he  was  suddenly  attacked 
by  osteomyelitis  of  the  fractured  bones,  which  necessitated  numer- 
ous incisions  for  the  liberation  of  pus  at  the  points  of  fracture. 
There  can  be  no  question  that,  in  this  case,  the  pus-microbes  entered 
the  circulation  at  the  primary  site  of  suppuration  and  were  arrested 
at  the  places  of  fracture,  where  they  found  favorable  conditions  for 
multiplication  and  caused  a  suppurative  inflammation  in  the  medul- 


LOCALIZATION    OF    MICRO-ORGANISMS.  47 

lary  tissue.  Practically  this  case  should  teach  us  that  in  a  patient 
who  has  sustained  a  simple  fracture  it  is  exceedingly  important  to 
guard  against  suppuration  in  any  part  of  the  body,  for  fear  that 
from  a  distant  purulent  focus  pus-microbes  may  enter  the  circula- 
tion and  cause  a  suppurative  osteomyelitis  of  the  broken  bone,  in 
the  same  manner  as  has  been  done  by  experiments  on  animals.  At 
the  same  time  and  place  I  examined  a  case  of  suppurative  strumitis 
due  to  a  similar  cause.  The  patient  was  a  man  of  about  forty  years 
of  age,  who  had  been  operated  upon  for  empyema  by  rib  resection 
some  time  ago.  He  had  had  a  large  goitre  since  childhood.  Im- 
provement after  the  operation  progressed  uninterruptedly  until  the 
empyema  was  nearly  well,  when  fever  set  in  and  the  right  side  of 
the  struma  became  painful  and  tender.  After  a  week  fluctuation 
was  well  marked,  and  a  free  incision  was  made,  which  gave  exit  to 
a  large  quantity  of  fetid  pus.  The  fever  subsided  promptly,  and 
the  case  again  progressed  favorably  until,  a  week  or  two  later,  the 
opposite  side  of  the  struma  was  attacked  in  a  similar  manner.  I 
was  present  when  this  side  was  incised.  A  large  amount  of  the 
same  green,  fetid  pus  escaped.  The  strumitis  was  unquestionably 
of  embolic  origin,  the  pus-microbes  which  gained  entrance  into  the 
circulation  from  the  pleural  cavity  found  in  the  struma  conditions 
which  favored  their  localization  and  growth,  to  be  followed  by  a 
suppurative  inflammation  of  the  swelling. 

Lebert  observed  secondary  or  metastatic  strumitis  develop  six 
times  in  connection  with  typhus,  once  with  puerperal  fever,  three 
times  after  pneumonia,  and  once  after  bronchitis.  Kocher  (u  Zur 
Pathologic  und  Therapie  des  Kropfes,"  Deutsche  Zeitschriflf.  Ohirur- 
gie,  B.  x.)  met  with  it  in  cases  of  typhus,  septic  endometritis,  and 
after  attacks  of  acute  gastro  intestinal  catarrh.  He  calls  special 
attention  to  the  fact  that  the  strumitis  almost  without  exception 
occurred  toward  the  close  or  after  the  subsidence  of  the  primary 
disease.  Kocher  believes  that  degenerative  changes  or  injuries  of 
the  struma  serve  as  predisposing  causes  for  the  arrest  of  pathogenic 
microbes  which  reach  the  organ  through  the  bloodvessels. 

Localization  of  Microbes  in  Antecedent  Pathological  Products. 

Antecedent  pathological  products  may  serve  the  same  purpose  in 
the  body  as  a  trauma  in  the  determination  of  localization  of  patho- 
genic microbes.  Suppuration  in  a  tumor,  or  a  hyperplastic  gland 
with  an  intact  cutaneous  covering,  indicates  that  in  the  tumor  or 
swelling  pus  microbes  have  been  arrested,  and  that  they  have  met 
with  a  soil  adapted  to  their  multiplication  and  the  exercise  of  their 
pathogenic  properties.  The  atypical  vascularization  in  tumors  and 
the  stenosis  of  the  lumen  of  bloodvessels  in  inflammatory  swellings 


48  LOCALIZATION    OF    MICKO-OKG  ANISMS . 

cannot  fail  in  furnishing  conditions  which  determine  filtration  of 
germ-containing  blood.  If  the  antecedent  pathological  product  is 
the  result  of  a  previous  infection  and  serves  as  a  medium  for 
localization  of  another  kind  of  pathogenic  germs,  we  speak  of  the 
combined  process  due  to  the  presence  of  two  varieties  of  micro- 
organisms as  a  mixed  infection.  The  first  positive  proof  of  the 
existence  of  such  secondary  processes  was  furnished  by  Brieger  and 
Ehrlich.  ("Ueber  das  Auftreten  des  malignen  Oedems  bei  Typhus 
abdominalis,"  Berl.  Min.  Wochenschrift,  1882,  No.  44.)  These 
observers  saw  a  malignant  oedema  develop  at  the  point  where  musk 
was  injected  hypodermatically  in  a  severe  case  of  typhoid  fever. 
They  found  that  in  such  cases  a  predisposition  is  produced  by  an 
existing  disease  to  the  growth  and  multiplication  of  microorgan- 
isms which  may  have  been  previously  present  in  the  organism 
without  producing  any  pathological  lesions.  Koch,  in  his  article 
on  u  Etiology  of  Tuberculosis/7  alludes  to  the  occurrence  of  mixed 
infections,  as  he  has  seen  at  the  same  time  bacilli  and  micrococci 
present  in  tubercular  products  Further,  he  has  observed  the 
bacillus  of  anthrax  side  by  side  in  the  same  tissues  and  has  seen 
micrococci  in  the  tissues  of  patients  suffering  from  typhus  fever. 
In  reference  to  the  occurrence  of  micrococci  in  tubercular  deposits 
in  the  lungs  and  spleen,  he  explained  their  presence  by  assuming 
that  they  entered  the  circulation  through  ulcerations  of  the  tongue, 
and  that  they  became  arrested  in  the  capillary  vessels  which  had 
lost  their  normal  resisting  power  by  the  tubercular  process. 

Samter  ("  Mischinfection  von  Tuberkelbacillen  u.  Pneumonie- 
kokken,"  Berl.  Min.  Wochenschrift,  1884,  No.  25)  discovered  in  the 
pneumonic  sputa  of  a  man  sixty-five  years  of  age,  who  previously 
had  suffered  from  a  latent  bronchial  catarrh,  besides  cocci  of  pneu- 
monia numerous  bacilli  of  tuberculosis.  The  necropsy  revealed 
old  tubercular  deposits  in  the  right,  and  more  recent  deposits  in 
the  left  lung,  and  around  the  latter  pneumonic  consolidation  of  the 
parenchyma  of  the  lung.  He  believed  that  the  pneumonic  foci 
furnished  a  favorable  soil  for  the  localization  and  growth  of  the 
bacillus  of  tuberculosis.  Heubner  and  Bahrdt  (aZur  Kenntniss 
der  Geleukeiterung  bei  Scharlach,"  Berl.  Min.  Wochenschrift,  1884, 
No.  44)  have  described  the  post-mortem  appearances  of  a  boy 
fourteen  years  of  age  who  had  suffered  from  multiple  suppurative 
synovitis  after  an  attack  of  scarlatina.  The  metastatic  suppura- 
tive process  could  be  traced  directly  to  a  circumscribed  purulent 
inflammation  of  the  right  tonsil  which  implicated  an  adjacent  vein, 
which  became  the  seat  of  a  purulent  thrombo-phlebitis,  and  the 
point  of  distribution  of  infective  emboli ;  chain  cocci  were  found 
in  the  pus  of  the  joints  and  even  in  the  patient's  blood. 

Frankel   and    Freudenberg  ("  Ueber  Infection   bei   Scharlach," 


LOCALIZATION    OF    MICRO-ORGANISMS.  49 

Centmlblatt  f.  klinische  Medicin,  1885)  cultivated  from  the  internal 
organs  of  three  patients  who  had  died  of  scarlatina  the  streptococ- 
cus pyogenes  and  looked  upon  the  presence  of  this  microbe  as  an 
evidence  that  a  secondary  infection  had  taken  place  through  the 
diseased  mucous  membrane  of  the  pharynx.  The  important  ques- 
tion presents  itself  whether,  in  cases  of  mixed  infection,  the  two 
kinds  of  microbes  enter  the  organism  at  the  same  time,  or  whether 
the  primary  infection  prepares  the  way  for  the  entrance  of  the 
microbes  which  produce  the  secondary  infection.  A  third  possi- 
bility might  be  maintained,  according  to  which  the  secondary 
infection  is  a  purely  accidental  occurrence,  as  was  claimed  by 
Brieger  and  Ehrlich.  Pus-microbes  being  present  at  all  times  and 
everywhere,  and  perhaps  gaining  entrance  into  the  body  more 
easily  than  others,  it  is  easy  to  understand  why  secondary  infection 
by  them  is  most  frequently  observed. 

Rosenbach  frequently  found  in  the  products  of  suppurative  in- 
flammation and  septic  processes  more  than  one  variety  of  pus- 
microbes.  He  frequently  met  with  both  kinds  of  staphylococci  in 
the  same  pus,  or  with  one  form  of  staphylococcus  and  the  strepto- 
coccus pyogenes. 

Loffler  ("Untersuchungen  iiber  die  Bedeutuug  der  Mikroorgan- 
ismen  fiir  die  Eutstehung  der  Diphtheric,"  Mittheilungen  aus  dem 
Reiclis-Gesundheits-Amte,  1884,  Band  ii.)  cultivated  from  the  mem- 
branes of  a  case  of  scarlatina-diphtheria  cocci  which,  when  in- 
jected into  the  circulation  of  animals,  produced  multiple  suppura- 
tive synovitis. 

Huber  ("  Experimentelle  Untersuchungen  iiber  Localisation  von 
Kraukheitstoffeu,"  Virchow's  Archiv,  Band  cvi.)  attributes  the 
occurrence  of  suppuration  and  gangrene  in  croupous  pneumonia, 
phlegmonous  inflammation  and  suppuration  in  erysipelas,  and  sup- 
puration in  tubercular  processes,  to  secondary  infection,  in  most 
instances  with  pus-microbes.  Schnitzler  ("  Combination  von 
Syphilis  und  Tuberculose  des  Kehlkopfes  "),  after  having  observed 
and  carefully  studied  a  number  of  cases,  has  come  to  the  conclu- 
sion that  syphilitic  ulceration  of  the  larynx  may  pass  into  tuber- 
cular, as  the  syphilitic  ulcer  furnishes  a  good  culture-soil  for  the 
bacillus  of  tuberculosis. 

Bumm  (Le  Bulletin  Medical,  December  25,  1887),  in  a  commu- 
nication to  the  Medical  Society  of  Munich,  discusses  a  theory  under 
the  name  of  mixed  infection,  which  he  describes  as  the  penetration 
into  the  organism  of  several  species  of  bacteria.  In  some  the  sec- 
ondary infection  is  purely  accidental,  as  for  example,  a  tuberculous 
patient  can  be  attacked  with  erysipelas,  a  lying-in  woman  suffering 
from  gonorrhoaa  may  become  the  subject  of  septic  infection. 
Another  and  practically  more  important  variety  of  mixed  infec- 

4 


50  LOCALIZATION    OF    MICRO-ORGANISMS. 

tion  he  speaks  of,  where  a  more  direct  relation  exists  between  the 
different  microbes,  in  the  sense  that  the  one  precedes  the  other  and 
prepares  the  soil  for  the  growth  of  the  latter.  These  forms  are 
characterized  by  being  constantly  associated  with  certain  definite 
microbes.  The  pneumococcus  may  prepare  the  soil  for  fructifica- 
tion of  the  bacillus  of  tuberculosis  or  the  microbes  of  suppuration 
in  individuals  that  otherwise  would  have  been  immune  to  the 
action  of  these  germs.  The  gonococcus  can  also  modify  the 
mucous  membrane  of  the  genito-urinary  tract,  chiefly  in  women,  in 
such  manner  as  to  render  easy  the  invasion  of  other  pathogenic 
microbes.  Gonorrhoeal  infection  of  the  vulvo-vaginal  glands  fur- 
nishes a  good  illustration  :  as  long  as  the  infection  remains  purely 
gonorrhoeal  the  acute  purulent  stage  is  succeeded  by  a  chronic 
stage  which  may  last  for  some  months,  the  swelling  gradually  sub- 
sides and  subsequently  atrophy  and  sclerosis  of  the  gland  follow. 
If,  however,  a  purulent  infection  is  added  to  the  gouorrhoeal  the 
gland  soon  becomes  enlarged  and  tender,  and  suppuration  follows. 
In  the  abscess  and  its  vicinity  no  gonococci  can  be  found  ;  the  pus 
only  contains  the  pyogenic  staphylococcus  which  has  exterminated 
the  gonococcus.  Cystitis  which  accompanies  gonorrhoea  is,  again, 
a  variety  of  mixed  infection.  The  stratified  epithelium  of  the 
bladder  is  impenetrable  to  the  gonococcus.  According  to  Bumm, 
the  cystitis  is  due  to  another  species  of  microbe  resembling  the 
gonococcus,  but  differing  from  it  by  taking  a  different  staining. 
The  gonococcus  expends  its  action  in  the  superficial  layers  of  the 
mucous  membrane  exclusively.  Suppurative  parametritis  following 
gonorrhoea  is  analogous  to  a  gonorrhoeic  bubo,  which  is  always 
caused  by  a  secondary  infection  with  pus-microbes. 

A  valuable  contribution  to  our  knowledge  of  mixed  infection  has 
recently  been  made  by  Babes  (Bacteriologische  Untersuehungen 
uber  septische  Processe  des  Kindesalters,  Leipzig,  1889),  of  Bucha- 
rest. His  investigations  consist  of  a  series  of  bacteriological  studies 
of  the  dead  bodies  of  children.  Within  a  few  hours  after  death 
tissue  was  taken  from  different  organs,  with  which  sterilized  culture 
material  was  inoculated,  the  strictest  antiseptic  precautions  being 
exercised  throughout.  In  acute  infectious  diseases,  such  as  diph- 
theria and  scarlatina,  he  found  the  spleen,  kidneys,  liver,  lungs, 
and  blood  infected  with  numerous  colonies  of  streptococci,  putre- 
factive bacteria,  capsule  cocci,  more  rarely  staphylococci  and 
various  bacilli.  Of  special  interest  are  his  researches  on  the 
manner  of  localization  and  extension  of  the  secondary  infection 
after  different  primary  diseases.  In  eight  cadavers  he  found  one 
or  more  species  of  bacteria  in  the  internal  organs.  In  a  case  of 
septic  omphalitis  he  found  the  bacillus  of  green  pus.  In  six  cases 
of  different  kinds  the  pus  streptococcus  grew  upon  the  culture 


LOCALIZATION    OF    MICKO-ORGANISMS.  51 

substances,  and  only  in  one  was  the  yellow  staphylococcus  found, 
and  in  five  cases  various  putrefactive  bacilli  were  cultivated.  In 
some  instances  he  was  able  to  demonstrate  the  point  at  which  the 
different  secondary  invasions  had  taken  place.  Thus  in  a  case  of 
sepsis  after  scarlatina  in  which  streptococci  were  found  in  every 
part  of  the  body,  a  pure  streptococcus  pneumonia?  was  found  in  the 
lower  part  of  the  left  lung,  while  a  number  of  foci  in  the  upper 
part  of  the  right  lung  contained  only  bacilli. 

Rinne  ( Verhandlungen  Deutscher  Naturforscher  und  Aerzte,  in 
Wiesbaden,  1887)  made  some  experiments  which  convinced  him 
that  a  trauma  which  results  in  an  ordinary  inflammation  does  not 
furnish  a  locus  minoris  resistentice  for  the  localization  of  pathogenic 
germs,  as  has  been  described  above.  He  claims  that  the  living 
body  possesses  the  capacity  to  eliminate  large  numbers  of  living 
pus-microbes  when  these  are  in  tissues  where  they  are  not  ex- 
posed to  direct  contact  with  oxygen.  He  has  found  that  cocci 
do  not  collect  at  points  the  seat  of  subcutaneous  injury,  and  that 
they  do  not  migrate  into  sterile  abscesses  from  distant  parts,  and 
not  even  after  intravenous  or  intraperitoneal  injection.  Even  an 
injection  of  a  pure  culture  of  pus-microbes  into  a  part  injured 
subcutaneously,  or  into  young  or  mature  cicatricial  tissue  around 
encapsulated  foreign  substances,  produced  no  suppuration.  From 
these  experiments  he  was  led  to  believe  that  tissue  lesions  which 
produce  an  inflammatory  reaction  do  not  predispose  to  metastatic 
suppuration.  On  the  other  hand,  it  was  also  demonstrated  ex- 
perimentally that  tissue  lesions  become  a  locus  minoris  resistentice 
after  the  tissues  have  become  permeated  by  the  chemical  products 
of  the  microorganisms.  The  locus  minoris  resistentice  for  the  pus- 
microbes  is  a  tissue  which,  by  chemical  or  by  chemical  and 
mechanical  lesions,  has  lost  its  normal  resistance  to  the  microbes, 
which  is  not  the  case  if  a  trauma  is  followed  by  an  active  repara- 
tive  process. 

The  same  author  ("  Der  Eiterungs- process  und  seine  Metastasen," 
Archiv  /.  klin.  Chirurgie,  Band  xxxix.  Heft  2)  has  recently  made 
numerous  experiments  on  rats,  rabbits,  guinea-pigs,  and  dogs,  to 
show  that  subcutaneous  mechanical  lesions  never  suppurate,  even 
after  inoculation  with  larger  doses  of  pure  cultures  of  pus-microbes. 
The  subcutaneous  lesions  were  made  with  a  tenotome  under  strict 
antiseptic  precautions  and  the  puncture  sealed  with  collodium. 
The  cultures,  usually  diluted  with  sterilized  water,  were  injected 
either  subcutaneonsly  into  the  peritoneal  cavity,  directly  into  the 
circulation,  or  into  the  injured  tissues,  but  metastatic  suppuration 
was  never  produced.  Circumscribed  suppuration  was  produced 
around  woollen  threads  impregnated  with  a  pure  culture  and  intro- 
duced into  the  tissues.  He  believes  that  in  these  cases  the  pus- 


52  LOCALIZATION    OF    MICRO-ORGANISMS. 

microbes  in  the  meshes  of  the  threads  produced  ptomaines,  which 
chemically  injured  the  tissues  before  they  could  be  removed  by  the 
tissues. 

When  chemical  abscesses  were  produced  by  the  injection  of  croton 
oil,  nitrate  of  silver,  ammonia  or  cadaverin,  and  the  animal  was  inocu- 
lated with  pns-microbes  in  another  part  of  the  body,  the  chemical 
pus  was  always  found  sterile.  The  same  was  observed  if  a  phleg- 
monous  inflammation  was  first  produced  and  one  of  the  chemical 
irritants  was  injected  later  in  some  distant  part  of  the  body. 

When  a  chemical  substance  which  produces  pus  is  injected  with 
pus-microbes  into  the  tissues,  the  former  prepares  the  soil  for  the 
latter,  but  does  not  determine  localization  of  microbes  introduced 
into  the  circulation.  The  cause  of  this  is  probably  the  active  cell- 
proliferation  produced  by  the  chemical  substance. 

Aschoff  ( Ueber  die  Einwirkung  des  Staphyloeoccus  pyogenes  aureus 
auf  Entzundetes  Gewebe  ;  Dissertation,  Bonn,  1889)  found  that  the 
action  of  pathogenic  microbes  upon  tissues  in  a  state  of  active  cell- 
proliferation  induced  by  chemical  irritants  is  intensified.  A  pure 
culture  of  the  yellow  coccus  was  injected  into  inflammatory  swell- 
ings, caused  by  the  subcutaneous  use  of  tincture  of  iodine.  The 
necrosis  and  exudation  were  much  more  marked  than  when  the 
same  injection  was  made  into  healthy  tissues,  while  the  regenera- 
tive processes  were  also  correspondingly  retarded  and  the  microbes 
manifested  greater  activity  and  power  of  resistance. 

Orlofif  ("  Materialieu  zur  Frage  iiber  die  Eintrittswege  der 
Mikroben  in  den  Thierischen  Organismus,"  Centralblatt  /.  Bac- 
teriologie  u.  Parasitenkunde,  B.  iii.  No.  15)  made  many  interesting 
experiments  to  ascertain  if  pathogenic  microorganisms  can  enter 
the  body  through  healthy  intact,  as  well  as  through  irritated 
diseased  mucous  membranes.  He  injected  a  pure  culture  of  the 
Staphyloeoccus  pyogenes  aureus  into  the  trachea,  duodenum,  and 
ileum  of  animals,  or  administered  the  same  culture  by  feeding. 
The  experiments  were  made  on  rabbits  and  guinea-pigs.  In  some 
of  the  animals  the  bronchial  mucous  membrane  was  altered  by 
application  of  croton  oil,  solution  of  nitrate  of  silver,  and  in  two 
instances  by  injuring  it  mechanically  with  a  catheter  through  a 
laryngotomy  wound  before  the  culture  was  injected.  The  same 
conditions  were  produced  in  the  stomach  and  intestines  by  similar 
means  prior  to  the  administration  of  the  culture.  In  12  experi- 
ments the  Staphyloeoccus  produced  no  symptoms  when  introduced 
into  the  healthy  stomach,  although  a  pure  culture  was  fed  for  from 
1  to  14  days.  In  the  post-mortems  made  12  to  72  hours  after  the 
feeding  of  the  microbes,  all  the  internal  organs  were  found  sterile, 
and  only  the  lower  portion  of  the  colon  contained  Staphyloeoccus 
colonies.  All  examinations  of  the  blood  during  life  yielded  nega- 


LOCALIZATION    OF    MICKO-ORG  ANISMS .  53 

tive  results.  In  7  experiments  in  which  the  stomach  was  irritated 
by  chemicals  before  the  feeding  of  the  culture  was  commenced,  6 
animals  remained  well,  and  in  the  one  that  died  the  microbes  had 
not  passed  beyond  the  prima  via,  as  the  blood  and  internal  organs 
were  found  sterile.  Of  12  animals  in  which  the  pure  culture  was 
injected  into  the  healthy  bronchial  tubes,  9  were  killed  one-half  of 
an  hour  to  11  days  after  the  injection,  and  3  died.  In  the  animals 
which  were  killed  no  trace  of  microorganisms  could  be  found  in 
the  blood,  they  had  not  passed  beyond  the  lung  tissue.  In  the  3 
fatal  cases  the  animals  died  17,  25,  and  70  hours  after  the  injec- 
tion, and  the  microbes  could  be  found  in  nearly  all  of  the  internal 
organs  and  the  blood.  In  the  2  cases  in  which  the  trachea  had 
been  altered  by  traumatic  irritation,  the  animals  were  killed  24  and 
25  hours  after  inoculation,  and  on  examination  it  was  seen  that  the 
infection  had  remained  local.  In  6  experiments  in  which  the  bron- 
chial tubes  were  irritated  with  a  solution  of  nitrate  of  silver  6 
hours  before  inoculation,  the  animals  died  20,  24,  40,  and  48  hours 
after  the  injection,  having  before  death  shown  evidences  of  serious 
pulmonary  trouble.  The  post-mortem  showed  in  all  of  them  pul- 
monary oedema  and  pleuritis,  but  staphylococci  were  found  in  only 
2  of  them  in  the  effusion.  In  6  animals  fed  on  the  culture,  in  4 
on  a  healthy  stomach  and  in  2  after  an  artificial  gastro-intestinal 
catarrh  had  been  produced,  he  made  a  subcutaneous  fracture,  and 
suppuration  followed  at  the  seat  of  the  fracture.  He  believes  that 
in  all  cases  in  which  the  microbes  entered  the  circulation  the  en- 
trance was  effected  through  some  perhaps  inappreciable  lesion. 

Gussenbauer  (Deutsche  Chiruryie  von  Billroth  u.  Luecke,  Lief.  4, 
p.  126)  describes  one  of  those  cases  which  are  not  of  infrequent 
occurrence  where  recovery  after  an  attack  of  suppurative  lymphan- 
gitis was  followed  by  a  phlegmouous  inflammation  in  the  axilla. 
The  patient  was  twenty-five  years  old,  in  good  health  otherwise, 
when  he  contracted  after  a  slight  injury  of  the  hand  a  lymphangitis 
and  lymphadenitis  of  the  arm  and  axilla  attended  by  circumscribed 
gangrene  of  the  skin  and  flexor  tendons.  The  lymphatic  glands 
did  not  suppurate  but  remained  slightly  enlarged.  Suppuration 
continued  for  eight  weeks  when  recovery  was  complete  and  the  man 
remained  in  good  health  for  eight  months.  At  this  time  he  suffered 
from  an  acute  abscess  in  the  axilla  of  the  same  side  which  could 
have  been  only  caused  by  the  pus-microbes  which  had  remained  in 
the  enlarged  lymphatic  glands  since  the  first  attack.  Smirnoff  has 
recently  published  an  interesting  dissertation  (St.  Petersburg, 
1889),  in  which  he  describes  his  examinations  of  syuovial  fluid 
removed  from  joints.  Pie  has  found  that  not  infrequently  in  the 
course  of  an  infectious  disorder  the  pathogenic  microbes  may  be 
detected  in  the  synovia.  He  examined  51  cases  including  erysipelas, 


54  LOCALIZATION    OF    MICKO-ORG  ANISMS . 

pneumonia,  abscess,  phthisis,  typhoid  fever,  diphtheria,  and  gonor- 
rhoea, while  in  some  the  result  was  negative,  in  others  not  only  was 
the  specific  microbe  present,  but  other  microorganisms  were  also 
detected,  showing  that  secondary  infection  had  occurred.  In  some 
lie  found  the  gonococcus  or  pneumococcus  with  the  staphylococcus  or 
streptococcus.  Transportation  of  the  microbes,  from  the  primary 
focus  to  the  joints,  occurred  either  by  way  of  the  bloodvessels  or 
lymphatics.  The  frequency  of  articular  infection  seems  to  be 
governed  by  the  size  and  form  of  the  bacteria.  The  small  round 
or  oval  cocci,  such  as  the  pneumococcus,  gonococcus,  and  pus- 
microbes,  obtain  more  ready  entrance  than  the  bacilli. 

in  many  instances  of  recurring  suppuration  years  after  the 
primary  injury  or  disease,  we  have  reason  to  believe  that  the 
microbes  were  introduced  with  a  foreign  body,  or  became  encapsu- 
lated in  the  granulation  tissue  during  the  healing  process,  and 
remained  there  in  a  latent  condition  until  by  some  accidental  cause 
the  surrounding  tissues  had  undergone  changes  favorable  for  their 
growth.  I  have  seen  numerous  cases  of  secondary  osteomyelitis 
ten  to  twenty-five  years  after  the  primary  attack,  which  occurred 
in  the  sclerosed  bone,  usually  near  one  of  the  epiphyseal  extremities. 
In  all  of  these  cases  the  disease  was  deeply  located,  the  primary 
starting-point  being  in  the  same  locality  as  in  the  first  attack.  A 
patient  who  has  once  suffered  from  osteomyelitis  during  childhood, 
is  always  prone  to  suffer  from  recurring  attacks,  and  the  disease, 
without  exception,  selects  the  old  site.  The  difficulties  which  deep 
cavities  in  bone  present  to  the  final  process  of  definitive  healing, 
offer  an  explanation  why  microbes  are  more  liable  to  become  buried 
and  permanently  retained,  than  in  suppuration  in  soft  parts. 

Nepveu  (Revue  de  Chirurgie,  1885,  p.  353)  reported  two  cases 
of  gunshot  injury  of  the  extremities  in  which,  fourteen  years  after 
the  definitive  healing,  suppuration  occurred  at  the  former  site  of 
injury. 

Numerous  instances  are  on  record  in  which  foreign  bodies  have 
remained  in  the  tissues  encapsulated  for  an  indefinite  period  of 
time  without  giving  rise  to  any  symptoms  until  the  microorganisms 
which  were  introduced  with  them  exercised  their  pathogenic  qualities, 
because  the  surrounding  tissues  had  undergone  changes  favorable 
to  such  a  process.  A  very  interesting  case  of  this  kind  is  reported 
by  Rinne  ("  Der  Eiterungs-process  und  seine  Metastasen,"  ArcMv. 
/.  Mm.  Chirurgie,  Band  xxxix.  p.  70).  In  1871,  a  man,  thirty- 
four  years  of  age  received  a  gunshot  wound  through  the  left  shoulder- 
joint.  Langenbeck  made  primary  resection  of  the  joint,  and  the 
wound  suppurated  for  a  number  of  weeks  profusely  but  healed 
completely  at  the  end  of  three  months.  The  patient  remained  in 
perfect  health  for  eleven  years,  when  he  was  suddenly  taken  with 


LOCALIZATION    OF    MICEO-O  KG  ANISMS.  55 

symptoms  of  acute  osteomyelitis.  When  admitted  {into  Friedrich- 
shain  Hospital  a  few  days  later  a  free  incision  were  made  over  the 
resected  end  of  the  humerus  and  a  large  quantity  of  fetid  pus 
escaped.  Free  drainage  and  disinfection  had  no  effect  in  diminish- 
ing the  severity  of  the  general  symptoms.  Through  another 
incision,  made  a  few  days  later,  small  particles  of  clothing  were 
removed.  As  the  symptoms  became  more  and  more  threatening 
amputation  was  made  through  the  shoulder-joint  four  weeks  after 
the  commencement  of  the  attack.  Patient  died  a  few  days  later 
after  well-marked  symptoms  of  pya3mia  had  manifested  themselves 
for  several  days. 

The  examination  of  the  amputated  arm  showed  old  foci  of  in- 
spissated pus  in  the  medullary  cavity  of  the  humerus,  which  leaves 
no  doubt  that  the  second  attack  of  osteomyelitis  was  caused  by 
microbes  which  had  remained  in  a  latent  condition  for  eleven 
years. 

Gussenbauer  (Deutsche  Chirurgie  von  Billroth  u.  Luecke,  Lief.  4, 
S.  125)  relates  two  such  cases.  In  one  a  bullet  perforated  through 
the  scapula  from  behind  and  lodged  in  the  deep  tissues.  The 
shoulder-joint  suppurated  and  had  to  be  resected.  The  bullet  could 
not  be  found.  The  wound  finally  healed  and  the  patient  remained 
well  for  twenty-three  years,  when  suppuration  occurred  at  the  site 
of  operation  ;  fragments  of  cloth  were  removed  through  an  incision 
and  the  man  recovered. 

At  a  recent  meeting  of  the  French  Congress  of  Surgeons,  Socin 
reported  a  case  that  had  come  under  his  observation,  in  which  a 
bullet  remained  in  the  tissues,  perfectly  encapsulated,  for  sixty 
years,  when  finally  the  pus-microbes  which  entered  the  organism 
with  it,  and  had  remained  all  this  time  in  a  latent  condition,  caused 
the  formation  of  an  abscess. 


CHAP  TEE   Y. 


ELIMINATION  OF  PATHOGENIC  MICROORGANSIMS. 

THE  probable  existence  of  pathogenic  microbes  in  the  healthy 
body,  and  the  spontaneous  subsidence  of  many  infective  processes, 
make  it  important  to  consider  the  ways  and  means  by  which  patho- 
genic microorganisms  are  rendered  harmless  in  the  living  body,  or 
are  removed  by  elimination  through  some  of  the  secretory  organs. 
It  is  not  at  all  improbable  that  the  localization  which  bacteria  effect 
may  come  to  play  an  important  part  in  the  study  of  micro-parasitic 
pathology.  Whatever  be  the  explanation,  there  is  no  doubt  that 
the  microorganisms  hitherto  found  have  various  relations  with  the 
tissues. 

In  all  infective  processes  in  which  life  is  not  destroyed,  and  the 
products  of  inflammation  do  not  find  their  way  to  the  surface 
spontaneously  or  by  treatment,  the  microbes  are  removed  with  the 
excretions  as  dead  foreign  bodies,  or  are  eliminated  through  some 
of  the  excretory  organs  in  an  active  state. 

1.  Phagocytosis. 

Metschnikoff  introduced  the  term  "  phagocytosis'7  to  designate 
the  destruction  of  microbes  within  the  organism  by  leucocytes  and 
the  fixed  tissue-cells. 

Wyssokowitsch  ("  Ueber  die  Schicksale  der  ins  Blut  injicirten 
Microorganismen  im  Korper  der  Warmbluter,"  7Jeitsohrift  f. 
Hygiene,  Band  i.  S.  1-45)  has  studied  experimentally  the  destiny 
of  microorganisms  injected  into  the  blood  of  warm-blooded  animals, 
and  found  that  they  were  not  eliminated.  He  demonstrated  by 
microscopical  examination  of  the  blood  and  by  cultivation  experi- 
ments, that  the  microbes  disappear  entirely  from  the  blood  or 
diminish  greatly  in  number  soon  after  intravenous  injection.  The 
saprophytes  disappear  soonest.  The  toxic  bacteria  are  slowest  in 
disappearing  and  seldom  leave  the  blood  entirely.  After  a  brief 
period,  when  their  number  is  at  a  minimum,  they  again  reappear 
in  the  blood  and  multiply  with  great  rapidity  until  they  kill  the 
animal.  Examination  of  the  urine  during  life  and  soon  after 
death  showed  that  elimination  of  bacteria  through  the  kidneys  did 
not  take  place ;  that,  on  the  other  hand,  the  urine  contained  bac-. 


PHAGOCYTOSIS.  57 

teria  ID  cases  in  which  extravasation  of  blood  into  the  parenchyma 
of  the  kidneys  had  taken  place.  During  the  first  few  hours  after 
intravenous  injection,  and  before  any  organic  changes  had  taken 
place  in  the  kidneys,  the  urine  contained  no  bacteria.  It  was  also 
shown  that  no  elimination  took  place  through  the  intestinal  canal, 
except  in  cases  in  which  the  mucous  membrane  was  the  seat  of 
hemorrhagic  extravasations,  or  other  serious  local  lesions.  In  two 
animals  infected  during  lactation,  the  milk  was  sterile,  showing 
that  no  elimination  took  place  through  the  mammary  gland. 
Microscopical  examination  revealed  an  increase  of  white  blood- 
corpuscles.  Inclusion  and  death  of  bacteria  in  blood-corpuscles 
were  not  observed.  The  bacteria  injected  into  the  circulation  soon 
became  deposited  in  certain  organs,  notably  the  spleen,  liver,  and 
medullary  tissue  of  bone,  and  consequently  separated  from  the  cir- 
culating blood.  Non-pathogenic  microbes  disappear  entirely  and 
permanently  from  the  blood  soon  after  injection.  The  spores 
retain  their  vitality  in  the  organism  for  an  unusually  long  time  ; 
for  instance,  active  spores  of  ordinary  mould  for  7  days,  and  the 
spores  of  the  bacillus  subtilis  for  62  to  78  days. 

Ribbert  (Der  Untergang  pathogener  Schimmelpilze  im  Korper, 
Bonn,  1887)  has  also  made  extensive  investigations  concerning 
the  fate  of  pathogenic  microbes  in  the  organism  when  introduced 
by  intravenous  injection.  In  rabbits  he  injected  into  the  circulation 
such  small  doses  of  a  pure  culture  of  aspergillus  flavescens  that  the 
animals  did  not  die  in  consequence  of  the  infection.  On  examining 
the  different  organs  at  variable  intervals  after  the  injection  it  was 
easy  to  determine  in  what  manner  the  germs  were  destroyed  or 
eliminated.  In  the  experiments  made  for  the  special  purpose  of 
ascertaining  the  fate  of  microbes  in  the  liver,  the  injection  was 
made  directly  into  one  of  the  mesenteric  veins.  In  all  other  cases 
the  injection  was  made  into  one  of  the  veins  of  the  external  ear. 
In  the  liver,  it  was  seen  that  when  the  microbes  reached  the  capil- 
lary vessels  and  the  terminal  branches  of  the  portal  vein  they  were 
surrounded  by  a  dense  cluster  of  leucocytes.  As  long  as  they 
remained  within  these  surroundings,  their  multiplication  appeared 
to  be  retarded.  Mitosis  was  not  observed  in  the  liver  cells  which 
were  compressed  by  the  inflammatory  exudation,  but  occasionally 
it  occurred  in  some  of  the  epithelial  cells  lining  adjacent  bile-ducts. 
The  microbes  were  seen  either  disappearing  directly  in  the  sur- 
rounding leucocytes,  or  some  of  the  liver  cells  were  transformed 
into  giant  cells,  into  the  protoplasm  of  which  they  found  their 
way,  and  they  were  destroyed.  The  giant  cells  either  undergo 
fatty  degeneration  and  disappear  with  their  contents  by  absorp- 
tion, or  they  are  again  transformed  into  normal  parenchyma  cells. 
When  larger  quantities  of  the  same  microbe  were  injected  no  such 


58      ELIMINATION   OF   PATHOGENIC    MICKO -ORGAN ISMS. 

aggregation  of  leucocytes  around  them  occurred  in  the  vessels  and 
tissues  of  the  liver,  and  multiplication  at  once  took  place,  and 
after  mural  implantation  of  the  microbes  had  taken  place  perfo- 
ration of  the  vessel  wall  was  effected  by  means  of  ray-like  pro- 
jections which  developed  from  the  microbes,  and  which  were  seen 
to  insinuate  themselves  between  the  cells.  If  the  animal  survived 
the  injection  for  a  few  days  the  rays  became  narrower  and  the 
granular  detritus  of  the  microbe  was  removed  by  giant  cells.  In 
studying  the  fate  of  the  same  microbes  in  the  lung,  the  injections 
were  made  either  into  a  vein,  the  trachea,  or  directly  into  the 
parenchyma.  The  microbes  surrounded  by  leucocytes  were  seen 
not  only  in  the  vessels  but  also  in  the  alveoli.  Limitation  of  the 
infection  and  the  final  destruction  of  the  microbes  were  here  also 
accomplished  by  the  leucocytes  and  giant  cells.  Injection  of 
larger  quantities  was  likewise  followed  by  rapid  permeation  of  the 
vessel  wall  by  the  microbes  and  their  early  appearance  in  the 
para  vascular  tissues.  In  the  kidneys  the  growth  of  the  microbe 
was  more  rapid  than  in  the  liver  and  lung,  the  rays  and  filiform 
projections  formed  earlier  and  developed  to  an  unusual  extent. 
The  accumulation  of  leucocytes,  on  the  other  hand,  was  retarded 
and  less  marked,  so  that  the  microbes  were  only  surrounded  by 
them  after  the  thread-like  projections  had  formed.  The  leucocytes 
containing  spores  were  not  only  found  in  the  interstitial  tissue,  but 
also  in  the  tubuli  uriniferi.  The  same  microbes  injected  into  the 
anterior  chamber  of  the  eye  produced  upon  the  iris  a  thin  layer  of 
fibrin,  in  which  the  leucocytes  gathered  around  the  microbes  in  the 
form  of  minute  nodules  and  the  microbes  were  soon  lost  in  their 
interior.  Only  a  slight  increase  of  growth  was  observed  in  this 
locality.  The  fixed  cells  of  the  iris  take  no  part  in  the  formation 
of  the  nodules,  and  the  work  of  destruction  of  the  microbes  is 
accomplished  exclusively  by  the  leucocytes.  Culture  experiments 
with  small  particles  of  organs  containing  the  microbe  showed  that 
their  power  to  infect  is  sometimes  lost  after  24  hours  and  always 
after  8  to  14  days.  The  retardation  and  arrest  of  germ-growth  by 
the  leucocytes  and  giant  cells  are  first  effected  mechanically,  but  to 
a  greater  extent  by  the  abstraction  of  oxygen.  It  is  also  possible 
that  the  diffusion  of  the  ptomaines  of  the  microbes  is  also  limited 
by  the  grouping  of  cells  around  centres  of  infection.  He  does  not 
believe  that  the  leucocytes  digest  the  microbes,  as  was  claimed  by 
Metschnikoff.  Fibrin-production  could  be  detected  by  Weigert's 
method  around  the  periphery  of  the  nodules.  Experiments  with 
aspergillus  fumigatus  yielded  the  same  results.  From  his  own 
work  Ribbert  has  come  to  the  conclusion  that  retardation  of  germ- 
growth  by  leucocytes  in  infectious  with  schizomycetes  is  an  estab- 
lished fact  in  pathology.  The  retarding  influence  of  the  organism 


PHAGOCYTOSIS. 


59 


to  germ-growth  differs  according  to  the  kind  of  germs,  as  the  germs 
by  the  production  of  noxious  substances  affect  the  envelopes  of  cells, 
and  most  of  the  pathogenic  microbes  assimilate  nutritive  material 
from  adjacent  tissues  more  readily  than  ordinary  mould. 

Microbes  which  diffuse  themselves  rapidly  and  which  do  not 
form  colonies  cannot  become  encapsulated  by  leucocytes.  By  count- 
ing the  blood-corpuscles,  it  was  found  that  after  injections  of  small 
doses  of  aspergillus  fluorescens  ten  times  more  leucocytes  were 
found  than  in  normal  blood.  Ehrlich's  method  of  staining  proved 
that  the  leucocytes  which  surrounded  the  spores  as  well  as  the  new 
corpuscles  in  the  blood  were  poly  nuclear  and  represented  the  pye- 
logenous  leucocytes.  In  animals  which  recovered  after  infection 
reinoculation  was  followed  by  more  prompt  encapsulation  of  the 
spores  by  the  leucocytes. 


FIG.  1. 


Leucocytes  of  frog  with  anthrax  bacilli.     (METSCHNIKOFF  ) 

Metschuikoff  ("  Ueber  den  Kampf  der  Zellen  gegen  Erysipel 
Kokken,"  Virchow's  Archiv,  B.  101,  p.  209),  who  was  the  first  to 
describe  the  struggle  of  the  cells  of  the  organism  against  invading 
microbes,  gives  the  name  of  phagocytes  to  the  cells  which  possess 
the  property  of  absorbing  and  digesting  microbes  (Fig.  1).  He 
made  his  researches  on  the  daphnia,  which  are  found  invaded  by  a 
parasite  of  the  higher  animals.  The  spores  of  this  parasite  peue 
trate  with  the  food  into  the  intestine,  from  which  they  escape  into 
the  cavity  of  the  body  of  the  daphnia.  As  soon  as  they  have  done 
so,  a  struggle  commences  between  them  and  the  white  corpuscles, 
which,  isolated  or  in  groups,  absorb  the  spore  and  destroy  and  trans  - 
form  it  into  shapeless  granules.  The  daphnia  is  thus  saved.  When 
the  victory  is  not  accomplished  the  spores  are  not  arrested  and 
destroyed  by  the  leucocytes,  and  they  invade  the  tissues  of  the 
animal  and  'kill  it.  Metschnikoff  affirms  that  the  same  struggle 
takes  place  in  the  higher  vertebrates  and  in  man  between  the 
microbes  and  the  cell-elements,  but  in  these  the  process  is  more 


60      ELIMINATION   OF   PATHOGENIC    MICRO-ORGANISMS. 

complicated,  as  there  are  two  kinds  of  phagocytes.  The  leucocytes 
he  calls  "  microphagi,"  and  to  the  permanent  tissue-cells  that  are 
capable  of  absorbing  minute  solid  bodies,  and  are  provided  only 
with  one  large  nucleus,  such  as  the  connective-tissue  cells,  epithelial 
cells  of  the  pulmonary  alveoli,  he  applies  the  term  u  macrophagi." 
In  infectious  diseases,  in  which  the  phagocytes  do  not  protect  the 
system  from  progressive  and  rapid  infection,  death  is  inevitable. 
In  anthrax  the  microphagi  are  powerless  to  absorb  the  bacteridia. 
The  case  is  different,  however,  when,  instead  of  a  strong  virus,  an 
attenuated  culture  is  employed.  Metschuikoff  employed  in  his 
experiments  a  watery  solution  of  vesuviu,  which  does  not  color 
living  microorganisms,  but  stains  dead  ones  brown.  In  this  way 
he  saw  most  of  the  rod-shaped  microorganisms,  encased  in  the  pro- 
toplasm of  the  microphagi,  assume  a  brown  color,  whereas  the  cells 
remained  unaffected  and  in  a  living  state. 

Hess  ("  Weitere  Untersuchungen  zur  Phagocytenlehre,"  Vir- 
chow's  Archiv,  B.  ex.  p  313)  has  examined  the  influence  exerted 
by  leucocytes  in  retarding  the  pathogenic  action  of  the  staphylo- 
coccus  pyogenes  aureus.  He  injected  a  minute  quantity  of  a  pure 
culture  of  this  microbe  into  the  substance  of  the  cornea  in  rabbits. 
The  eyes  were  extirpated,  hardened,  and  examined  microscopically 
"24:  hours  to  8  days  after  inoculation.  During  the  first  24  hours  the 
cocci  multiplied  very  rapidly  at  the  point  of  infection ;  36  hours 
after  inoculation  leucocytes  were  seen  enclosing  the  infected  area, 
and  all  of  them  contained  microbes.  As  the  suppurative  process 
advanced  the  intra-cellular  cocci  increased  in  number.  Gradually 
the  cocci  disappeared  in  the  cells,  and  after  the  sixth  day  often 
none  could  be  found.  The  free  cocci  in  the  tissues  formed  a  very 
narrow  zone  around  the  margins  of  the  ulcer,  while  the  microbe- 
carrying  leucocytes  were  found  in  the  tissues  at  a  greater  distance. 
In  two  cases  which  terminated  fatally,  an  extensive  hypopyum 
formed  and  no  phagocytosis  had  occurred,  although  many  leuco- 
cytes were  present.  In  one  experiment  on  a  cat,  the  ulcer  resulting 
from  the  inoculation  was  very  small,  and  in  this  instance  phagocy- 
tosis was  more  marked  than  in  the  rabbits.  In  the  destruction  of 
the  cocci  in  the  ulcer,  the  cells  springing  from  the  conjunctival  sac 
played  also  an  important  part,  and  the  secretions  from  the  conjunc- 
tiva contained  soon  after  the  inoculation  many  cells  with  microbes 
in  their  protoplasm.  Warm  fomentations  at  first  appeared  to  favor 
the  increase  of  microbes,  but  later,  by  stimulating  the  action  of  the 
phagocytes,  they  retarded  it. 

Christmas-Dircking-Holrnfeld  ("  Ueber  Immunitat  und  Phago- 
cytosis," Fortschritte  der  Medicin,  No.  13,  1887)  repeated  the 
experiments  of  Metschuikoff,  and  claimed  that  in  animals  immune 
to  anthrax,  or  rendered  artificially  immune,  the  bacillus  when 


PHAGOCYTOSIS.  61 

introduced  into  the  tissues  is  devoured  by  the  leucocytes.  He 
experimented  with  a  very  virulent  culture  aud  cultures  attenuated 
by  age,  or  by  Koch's  method  of  attenuation.  These  experiments 
were  made  on  mice,  rabbits,  and  young  and  old  rats.  He  soon 
found  out  that  the  results  were  greatly  modified  by  the  degree  of 
susceptibility  of  the  animal  to  the  anthrax  bacillus.  In  animals 
very  susceptible  to  the  disease,  as  in  mice  and  rabbits,  the  inocula- 
tion of  a  very  active  culture  produced  little  or  no  inflammatory 
reaction  at  the  point  of  inoculation.  In  animals  with  a  greater 
degree  of  immunity,  as  young  rats,  the  injection  produced  suppura- 
tion at  the  point  of  inoculation,  which  assumed  the  character  of  an 
abscess,  as  the  susceptibility  was  diminished  as  in  old  rats.  The 
injection  of  a  mitigated  culture  produced  suppuration  even  in 
rabbits.  The  intensity  of  the  inflammatory  reaction  following  the 
inoculation  with  the  bacilli  of  anthrax  stood  in  an  inverse  ratio  to 
the  degree  of  the  susceptibility  of  the  infected  animal.  The  bacilli 
were  never  found  in  the  interior  of  the  pus-corpuscles,  and  it 
followed  as  a  natural  conclusion  that  death  and  disintegration 
were  effected  by  the  pus  serum.  That  the  pus-corpuscles  did  not 
destroy  the  bacilli  was  also  proved  by  another  experiment.  A 
pure  culture  of  anthrax  bacilli  was  put  in  hermetically-sealed  glass 
tubes  containing  pus,  which  when  kept  at  the  temperature  of  the 
body  killed  the  bacilli  in  from  two  to  three  days.  Metschnikoif 
asserts  that  the  latter  observation  does  not  prove  that  the  pus-cor- 
puscles did  not  act  the  part  of  phagocytes,  as  under  the  conditions 
described  they  might  have  retained  the  properties  of  such. 

Wehr  ("  Ueber  den  Untergang  des  Staphylococcus  pyogenes 
aureus  in  den  durch  ihn  hervor-gerufenen  Entzuudungs-processen 
in  der  Lunge,"  Dissertation,  Bonn,  1887)  injected  pure  cultures  of 
the  Staphylococcus  pyogeues  aureus  into  the  trachea  of  rabbits  and 
favored  the  descent  of  microbes  into  the  finer  divisions  of  the  bron- 
chial tubes  by  standing  the  animals  for  some  time  upon  the  hind 
legs.  Soon  after  the  injection  he  found  cocci  not  only  in  the  inte- 
rior of  leucocytes  which  had  grouped  around  the  seat  of  injection, 
but  also  in  the  interior  of  epithelial  cells.  He  assigns  to  epithelial 
cells  phagocytic  action.  During  the  first  week  after  injection  he 
found  cocci  without  exception  in  the  epithelial  cells.  In  none  of 
his  experiments  could  the  microbes  be  found  in  the  blood  or  in  any 
of  the  internal  organs. 

The  doctrine  of  phagocytosis  has  recently  received  a  substantial 
support  from  the  researches  of  Nuttal  and  Buchner  ("Uber  die  bak- 
terienodtende  Wirkung  des  Zellenfreien  Blutserums,"  Centralblatt  f. 
BaUeriologie  u.  Pamsitenkunde,  B.  v.-No.  25).  These  researches 
show  that  not  only  the  cellular  elements  of  the  blood  are  antago- 
nistic to  pathogenic  bacteria,  but  that  the  serum  possesses  a  similar 


62      ELIMINATION   OF   PATHOGENIC   MICRO -O  EGA  N  IS  MS. 

destructive  power.  Their  experiments  with  different  microbes 
showed  that  both  defibrinated  and  freshly-drawn  blood  manifest  a 
decidedly  deadly  action  upon  them  for  more  than  four  hours  after 
it  has  been  drawn  from  the  body.  For  example,  the  number  of 
anthrax  bacilli  in  a  given  quantity  of  material  was  reduced  in  two 
hours  from  4800  to  56,  by  being  mixed  in  a  test-tube  with  defib- 
rinated blood;  and  three  hours  later  only  3  living  bacilli  re- 
mained. The  destructive  action  of  the  blood  on  putrefactive  bac- 
teria is,  however,  much  less  marked,  and  against  some  of  them,  at 
least,  the  blood  manifested  little  or  no  germicidal  action. 

Ribbert  ("Ueber  den  Verlauf  der  durch  Staphylococcus  aureus  in 
der  Haut  von  Kauiuchen  hervorgerufenen  Entzundung,"  Deutsche 
Wochenschrifi,  No.  6,  1889)  studied  experimentally  the  phago- 
cytic  action  of  leucocytes  in  the  tissues  infected  with  pus-microbes. 
He  made  the  skin  of  rabbits  over  a  limited  area  aseptic,  and  made 
inoculations  with  pus-microbes  by  introducing  a  pure  culture  of 
the  yellow  coccus  through  punctures  made  with  a  cataract-needle. 
In  cases  where  the  small  wound  healed  rapidly  he  found  on  exam- 
ining the  tissues  that  even  during  the  course  of  the  first  day  all 
of  the  microbes  had  reached  the  interior  of  the  leucocytes  and 
fixed  connective-tissue  cells  and  showed  signs  of  destructive 
changes.  Later  the  cocci  disappeared  completely.  Thirty-six 
hours  after  inoculation  he  found  distinct  mitotic  changes  in  the 
connective-tissue  cells  within  and  in  the  immediate  vicinity  of  the 
inflammatory  focus  and  somewhat  earlier  in  the  epithelial  cells. 
If  suppuration  occurred  he  found  a  considerable  aggregation  of 
leucocytes,  which  apparently  were  being  destroyed  by  the  cocci, 
consequently  phagocytosis  was  not  present ;  on  the  other  hand,  the 
cocci  underwent  destructive  changes  to  the  fourth  day,  and  were 
then  taken  up  by  the  macrophagi.  The  death  of  the  cocci  under 
these  circumstances  was  not  caused  by  the  phagocytes  but  was 
owing  to  the  exclusion  of  oxygen  or  other  nutrient  material  by  the 
wall  of  cells  in  their  vicinity. 

Ruffer  ("  Notes  on  the  Destruction  of  Microorganisms  by  Amoe- 
boid Cells,"  British  Medical  Journal,  August  30,  1890)  is  a  firm 
believer  in  the  phagocytic  action  of  leucocytes  and  other  amoeboid 
cells.  He  first  studied  sections  of  the  Peyer's  patches  of  rabbits, 
removed  with  antiseptic  precautions,  plunged  at  once  into  absolute 
alcohol,  and  then  stained  with  carmine  and  gentian-violet.  He 
often  found,  crowded  in  between  the  layer  of  epithelial  cells  in 
the  inner  surface  of  the  mucous  membrane,  leucocytes  holding 
microorganisms  in  their  protoplasm.  In  the  submucous  tissue  he 
also  found  lymphoid  cells  enlarged  to  the  size  of  the  so-called 
epithelioid  cells.  He  also  found  leucocytes  in  the  interior  of  the 
macrophagi.  He  asserts  that  the  leucocytes  wander  out  to  the 


ELIMINATION    THEOUGH    KIDNEYS.  68 

surface  of  the  mucous  membrane,  seize  the  microorganisms,  and 
bring  them  back  to  be  destroyed  by  the  large  phagocytes.  Even 
the  large  cells  in  some  lymphoid  structures  may  wander  to  the 
surface  and  absorb  and  destroy,  microbes.  He  is  of  the  opinion 
that  the  action  of  the  microorganisms  taking  place  in  the  normal 
lymphoid  tissues  of  the  alimentary  tract  resembles,  in  all  particulars, 
the  destructive  process  following  on  the  inoculation  of  pathogenic 
organisms  into  resistant  animals. 

The  author  asserts,  from  further  experiments,  that  the  large 
epithelioid  cells  of  the  spleen,  lymphatic  glands,  and  those  of  the 
lungs,  are  really  macrophagi  developed  from  the  lymphoid  cells. 

Lubarsch  ("  Ueber  Abschwachuug  der  Milzbrand-bacillen  im 
Froschkorper,"  Fortschritte  der  Medicin,  No.  4,  1888),  in  his  ex- 
periments on  frogs  with  the  anthrax  bacillus,  infected  the  animals 
by  inserting  into  the  lymph  sac  portions  of  the  internal  organs  of 
animals  which  had  died  of  anthrax.  His  observations  led  him  to 
the  conclusion  that  the  phagocytes  in  reality  do  devour  the  mi- 
crobes, and  that  disintegration  of  the  iutra-cellular  microbes  is  an 
active  process  on  the  part  of  the  cells. 

2.  Elimination  of  Microbes  through  the  Kidneys  and  other  Organs. 

The  rapidity  with  which  some  microbes  disappear  from  the 
blood  is  very  remarkable ;  it  is  in  many  cases  a  matter  of  minutes, 
certainly  of  an  hour  or  two,  and  this  disappearance  from  the  blood 
must  be  due  to  an  active  process  on  the  part  of  the  constituents  of 
the  blood  on  them.  Mere  unsuitability  of  soil  is  not  sufficient  to 
account  for  the  rapidity  of  the  phenomenon.  That  they  are  elimi- 
nated through  the  kidneys  is  shown  by  various  observations,  and 
this  is  an  important  point  to  remember,  as  probably  explaining 
certain  cases  of  pyelitis  occurring  in  patients  who  have  never  had 
any  instrument  passed,  and  in  whom  urethra  and  bladder  are  per- 
fectly normal.  The  salivary  glands,  more  especially  the  parotid, 
occasionally  take  part  in  the  excretion  of  pus- microbes,  thus  offer- 
ing an  explanation  of  the  not  infrequent  occurrence  of  abscesses  in 
the  parotid  gland  after  suppurations  elsewhere. 

Rosenstein  ("  Vorkommen  der  Tuberkel-Bacillen  im  Harn,n 
Centralblatt  f.  d.  med.  Wissensch.,  1883,  No.  5)  and  Babes  (Fort- 
schritte der  Medicin,  B.  i.  p.  4)  found  bacilli  in  the  urine  in 
patients  suffering  from  tuberculosis  of  the  gemto-urinary  tract. 

Fardel  ("  Les  bacilles  dans  la  tuberculose  miliaire.  Tuberculose 
glomerulaire  dti  rein,"  Archiv  de  Physiologie,  1886)  mentioned  the 
condition  of  the  kidneys  in  cases  of  miliary  tuberculosis  as  an 
evidence  that  the  bacilli  are  diffused  through  the  bloodvessels. 
He  found  in  a  thrombosed  capillary  vessel  in  a  glomerulus,  in 


64      ELIMINATION   OF   PATHOGENIC    MICRO-ORGANISMS. 

which  no  inflammatory  changes  had  as  yet  occurred,  numerous 
bacilli.  They  were  also  found  in  the  epithelial  cells  of  a  convo- 
luted capillary  vessel.  The  author  was  also  able  to  demonstrate 
that  the  deposits  in  the  kidney  occurred  around  the  capillary  ves- 
sels in  the  glomeruli,  often  including  the  latter  completely.  He 
believes  that  the  bacilli  migrate  from  the  glomeruli  into  the  sur- 
rounding tissue,  when  they  give  rise  to  miliary  nodules.  In  cases 
of  tuberculosis  of  the  kidneys  the  number  and  arrangement  of  the 
bacilli,  as  they  are  found  in  the  urine,  are  characteristic  of  this 
disease. 

Moupurgo  (Schmidt's  Jahrbucher,  B.  ccxii.  p.  128)  found  in  the 
urine  of  a  woman  suffering  from  renal  tuberculosis  numerous 
bacilli  arranged  in  groups  resembling  the  letter  "  S,"  an  appear- 
ance which  is  only  observed  in  pure  cultures.  Koch  described  this 
bacteriological  condition  in  a  case  of  miliary  tuberculosis.  For 
such  a  culture  to  form  in  the  genito-uriuary  apparatus,  it  is  neces- 
sary that  the  bacilli  should  be  located  in  a  place  where  they  are 
not  washed  away  by  the  urine,  and  where  they  find  favorable  soil 
for  their  growth,  conditions  which  are  only  furnished  in  the 
kidney. 

Neumann  ("Ueber  die  diaguostische  Bedeutung  der  Bakterio- 
logischen  Untersuchungen  bei  inneren  Krankheiten,  Berl.  Idin. 
Wochensehrift,  Nos.  7,  8,  9,  1888)  found  the  specific  microbes  in 
the  urine  in  cases  of  typhus,  septicaemia,  and  pyaemia.  In  a  case 
of  acute  endocarditis  and  acute  osteomyelitis,  he  cultivated  from 
the  urine  the  staphylococcus  pyogenes  aureus.  He  believes  that 
the  microorganisms  which  circulate  in  the  blood  localize  in  the 
capillary  vessels  of  the  kidney,  where  they  often  cause  minute, 
multiple  lesions  without  implication  of  the  entire  parenchyma  of 
the  organ.  Through  the  altered  tissues  some  of  the  microbes  enter 
the  tubuli  uriniferi  and  are  eliminated  with  the  urine. 

Seitz  found  the  bacillus  of  typhus  in  the  urine  in  2  out  of  7 
cases,  Konjajeff  in  3  out  of  20  cases,  and  Hueppe  only  once  in  16 
cases,  Neumann  in  8  out  of  48  cases.  The  last  observer  ("Ueber 
Typhus  Bacillen  irn  Urin,"  Berl.  Jclin.  Wochenschrift,  February  10, 
1890)  in  some  instances  found  them  so  numerous  that  under  the 
microscope  the  urine  appeared  like  a  fluid  culture.  In  these  cases 
the  bacillus  multiplies  in  the  bladder.  In  two  cases  he  also  found 
the  streptococcus  pyogenes,  an  occurrence  which  he  considered  as 
an  evidence  of  the  existence  of  complications. 

Philipowicz  (u  Ueber  das  Auftreten  pathogener  Microorgau- 
ismen  im  Harue,"  Wiener  med.  Blatter,  1885,  No.  22)  found  the 
bacillus  of  tuberculosis  not  only  in  three  cases  of  tubercular  pyelo- 
nephritis, but  also  in  cases  of  acute  miliary  tuberculosis.  If  the 
organisms  were  not  present  in  sufficient  number  for  detection  by 


ELIMINATION    THROUGH    KIDNEYS.  65 

the  microscope,  their  presence  in  the  urine  could  be  proved  by  the 
injection  of  the  urine  into  the  peritoneal  cavity  of  guinea-pigs. 
He  also  found  bacilli  in  the  urine  in  cases  of  glanders.  In  mice 
which  had  died  of  anthrax,  the  urine  contained  the  bacilli  in  large 
numbers.  In  patients  who  had  succumbed  to  ulcerative  endocar- 
ditis, pus-microbes  were  also  found  in  the  urine. 

Schweiger  ("Ueber  das  Durchgehen  von  Bacillen  durch  die 
Nieren,"  Virchow's  Archiv,  B.  c.  Heft  2)  has  shown  conclusively 
by  his  careful  clinical  observations  that  the  urine  from  scarlatinal 
patients  is  contagious ;  for  varicella,  typhus  recurreus,  and  malaria 
the  same  holds  true.  In  typhus  Gaff  ky  has  found  bacilli  in  the 
vessels  of  the  kidneys.  As  in  most  infective  diseases  the  kidneys 
show  textural  changes,  it  was  natural  to  conclude  that  the  renal 
lesions  were  caused  by  microbes  on  their  way  out  of  the  body. 
Schweiger  looks  upon  all  kidney  lesions  found  in  the  course  of 
infective  diseases  as  of  bacillary  origin.  To  prove  that  microbes 
pass  through  the  kidneys,  he  cultivated  a  bacillus  which  Reimann 
had  discovered  in  the  pus  of  ozaBna.  This  bacillus  is  stained  an 
intense  green  color  in  a  culture  of  gelatin  and  agar  after  twenty- 
four  hours.  The  cultures  of  this  green  bacillus  were  suspended  in 
a  sterilized  physiological  solution  of  salt,  and  injected  directly 
into  the  circulation.  The  experiments  were  made  on  a  dog,  cat, 
and  rabbit.  The  bacillus  did  not  pass  directly  through  the  kid- 
neys, but  a  certain  length  of  time  intervened  between  the  injection 
and  its  appearance  in  the  urine,  as  though  somewhere  an  obstacle 
to  its  free  passage  had  been  met  with.  At  first  only  isolated 
bacilli  were  found  in  the  urine,  but  later  in  large  numbers.  In 
one  instance  he  extirpated  one  kidney,  and  two  days  later,  during 
the  first  stage  of  compensatory  hypertrophy  of  the  remaining 
organ,  he  injected  a  culture  directly  into  the  carotid  artery.  The 
animal  died  suddenly  two  and  a  half  hours  after  the  injection  in 
an  attack  of  convulsions.  Under  strict  antiseptic  precautions  the 
urine  was  removed  from  the  bladder,  and  with  it  a  culture  of  agar- 
agar  was  inoculated.  The  next  day  the  culture  showed  a  beautiful 
growth  of  the  same  bacillus.  The  author  believes  that  the  kidney, 
the  seat  of  increased  vascular  pressure,  furnished  a  favorable  con- 
dition for  the  rapid  passage  of  the  microbe.  He  found  the 
microbes  most  frequently  in  the  glomeruli,  and  in  the  space  be- 
tween these  and  Bowman's  capsule;  and  again,  quite  abundant  in 
the  bloodvessels  and  in  the  lumen  of  the  first  portion  of  the  con- 
voluted tubuli  uriniferi,  and  only  rarely  in  the  perivascular  con- 
nective tissue.  Only  once  a  bacillus  was  found  between  two  epithe- 
lial cells  of  the  convoluted  tubules.  In  the  cells  themselves  no 
bacilli  were  found.  Upon  these  observations  he  bases  his  advice  to 
favor  elimination  of  microbes  through  the  kidneys  in  all  infective 

5 


66      ELIMINATION   OF   PATHOGENIC   MICRO-ORGANISMS. 

processes  by  administering  large  quantities  of  water,  and  even 
diuretics. 

Escherich  ("  Bacteriologische  Untersuchungen  iiber  Frauen- 
milch,"  Fortschritte  der  Medicin,  B.  iii.  p.  231)  examined  the  milk 
for  bacteria  in  patients  suffering  from  puerperal  infection,  and, 
without  exception,  found  that  it  contained  the  staphylococcus 
pyogenes  aureus  or  albus.  After  having  satisfied  himself  by  the 
examination  of  twenty-five  healthy  cases  that  normal  milk  con- 
tained no  microorganisms,  he  examined  the  milk  of  such  patients 
whose  bodily  temperature  was  increased  by  puerperal  processes,  or 
lactation,  who,  in  fact,  presented  evidences  of  septic  conditions, 
and  here  he  found  regularly  micrococci  present  in  the  milk,  prin- 
cipally the  staphylococcus  aureus  and  albus.  In  puerperal  women, 
who  had  fever  from  other  causes,  such  as  pulmonary  tuberculosis, 
otitis  media,  etc.,  no  microorganisms  were  found  in  the  milk.  He 
believes  that  the  microbes  are  introduced  into  the  milk  through 
the  blood,  which  they  enter  in  puerperal  septicaemia,  through 
wounds  or  abrasions  of  the  genital  tract. 

Bumm  ("  Zur  Aetiologie  der  puerperalen  Mastitis,"  Archiv  f. 
Gf-yndkologie,  B.  xxiv.  p.  262)  cultivated  from  a  case  of  puerperal 
mastitis  a  diplococcus  which  resembled  the  gonococcus  very  much. 
He  injected  the  culture  under  his  own  skin,  and  produced  an 
abscess.  Karliuski  injected  a  pure  culture  of  staphylococcus  pyo- 
geues  aureus  into  a  vein  of  a  puerperal  rabbit  on  the  third  day 
after  labor.  In  twenty-four  hours  the  animal's  milk  proved  to  con- 
tain numerous  staphylococci.  On  the  fourteenth  day  the  animal 
died  of  pyaemia. 

Bolliuger  ("  Ueber  Tuberkelbacillen  im  Euter  einer  tuberku- 
losen  Kuh,  und  iiber  die  Yirulenz  des  Secretes  einer  derartig 
erkraukten  Milchdriise."  Bayr.  Arztl.  Intelligenzblatt,  1883,  No. 
16)  found  tubercle  bacilli  in  the  parenchyma  of  the  udder,  as  well 
as  in  the  secretion  in  the  milk  ducts  in  a  cow  suffering  from  tuber- 
culosis, which,  on  being  inoculated  in  guinea-pigs,  produced  typi- 
cal tuberculosis. 

Hirschberger  (Archiv  f.  Idin.  Medicin,  June,  1889)  has  made 
some  very  interesting  investigations  in  reference  to  the  presence  of 
tubercle  bacilli  in  the  milk  of  tuberculous  cows.  The  material 
was  furnished  by  the  abattoir  of  Munich,  and  the  examinations 
were  made  in  Bellinger's  laboratory.  The  whole  udders  of  cows 
that  were  known  to  be  tuberculous  were  sent  to  the  laboratory, 
where,  under  the  strictest  antiseptic  precautions,  the  milk  ducts 
were  opened  and  the  milk  removed  was  injected  into  the  peritoneal 
cavity  of  guinea-pigs.  Twenty  inoculation  experiments  were 
made  in  as  many  animals,  and  in  eleven,  or  in  fifty-five  per  cent., 
the  result  was  positive.  In  most  of  those  cases  the  disease  ap- 


ELIMINATION    THKOUGH    KIDNEYS.  67 

peared  as  a  diffuse  rniliary  tuberculosis  of  the  peritoneum,  omen- 
turn,  spleen  and  liver;  the  milk  of  cows  suffering  from  advanced 
tuberculosis  proved  the  most  virulent. 

Ernst  (Medical  News,  Sept.  28,  1889)  examined  114  samples  of 
milk  obtained  from  36  cows  suffering  with  tuberculosis  of  some 
organ  other  than  the  udder;  17  samples  were  found  to  contain  the 
specific  bacillus.  These  17  specimens  came  from  10  cows. 

Inoculation  with  the  infected  milk  produced  the  disease  in  50 
per  cent,  of  the  cases  treated.  Feeding  experiments  were  also 
made,  with  the  result  of  inducing  the  disease  in  a  number  of  calves 
and  young  pigs.  These  experiments  furnish  positive  proof  that 
the  bacillus  of  tuberculosis  is  eliminated  through  the  mammary 
secretion  even  in  cases  where  the  gland  is  not  the  seat  of  any  tuber- 
cular lesion. 

Ribbert  found,  twenty-four  hours  after  injecting  osteomyelitic 
cocci  directly  into  the  circulation  of  animals,  the  microbes  in  all  of 
the  internal  organs  ;  later,  only  in  the  kidney.  Liibbert  found  the 
staphylococci  in  osteomyelitis  frequently  in  the  urine.  Lebedoff 
saw  the  streptococcus  of  erysipelas  in  the  skin  and  umbilical  cord 
of  a  child  born  eight  days  after  its  mother  had  recovered  from  an 
attack  of  erysipelas. 

Clinical  observation  as  well  as  experimental  research  has  shown 
that  in  all  localized  infective  processes  the  leucocytes  act  as  an 
advance-guard  in  protecting  the  tissues  against  the  ingress  of  the 
microbes  by  mechanically  obstructing  the  way ;  later,  the  active 
granulation  tissue  performs  the  same  function.  As  inclusion  of  the 
microbe  in  the  cell  protoplasm  may  have  a  great  deal  to  do  with  the 
destruction  of  the  microbes,  it  is  correct  to  speak  figuratively  of  a 
struggle  of  cells  against  microbes.  When  the  microbes  have 
become  disseminated  throughout  the  organism  by  the  circulating 
blood,  they  are  also  brought  to  the  excretory  organs,  through  which 
many  of  them  are  eliminated  without  having  lost  their  virulence 
during  the  passage  through  the  body. 


CHAPTEE    VI. 


ANTAGONISM  AMONG  MICROORGANISMS. 

ONE  of  the  most  recent  achievements  in  bacteriology  is  the  dis- 
covery of  the  antagonism  which  exists  among  certain  pathogenic 
microorganisms.  That  such  antagonism  exists  has  been  demon- 
strated by  cultivation,  and  inoculation  experiments. 

Pawlowsky  (Virchow's  Archiv,  B.  cviii.)  has  furnished  strong 
experimental  evidence  of  the  antagonism  which  exists  between  the 
pneumococcus  of  Friedlander  and  the  bacillus  of  anthrax ;  as,  in 
eight  rabbits  infected  with  a  fatal  dose  of  anthrax,  all  of  the  animals 
were  saved  by  a  subsequent  injection  of  a  pure  culture  of  the  pueu- 
mococcus.  The  same  author  also  ascertained  that  the  micrococcus 
prodigiosus  is  also  antagonistic  to  the  coccus  of  erysipelas.  Thus, 
ten  rabbits  were  first  inoculated  with  anthrax  bacilli,  and  then  cul- 
tivations of  the  micrococcus  prodigiosus  were  injected  subcuta- 
neously  into  each  animal  on  two  occasions,  two  and  twenty-four 
hours  after  injection  ;  of  these  ten  animals,  eight  recovered.  He 
also  found  that  subcutaneous  injection  of  anthrax  bacilli,  and  cul- 
tivations of  pneumonococci  were  fatal  to  rabbits ;  and  that  subcu- 
taneous injection  of  cultivations  of  anthrax  bacilli  and  staphylo- 
coccus  pyogenes  aureus  was  not  followed  by  the  death  of  the 
animal ;  four  rabbits  treated  with  a  culture  of  the  staphylococcus 
aureus  recovered  ;  of  seven  anthracic  rabbits  treated  by  subcuta- 
neous injection  of  a  culture  of  streptococcus  erysipelatosus,  two 
died. 

Emmerich  (Fortschritte  der  Medioin,  B.  v.  1887)  has  also  studied 
experimentally  the  antagonism  among  pathogenic  microbes  in  the 
living  organism.  His  experiments  on  rabbits  have  shown  the 
value  of  the  erysipelas  cocci  as  a  protective  and  curative  agent  in 
anthrax  in  these  animals.  In  one  series  of  experiments  the  rab- 
bits were  first  inoculated  with  a  large  quantity  of  a  reliable  culture 
of  the  streptococcus  of  erysipelas,  and  then,  two  to  fourteen  days 
later,  the  animals  were  again  inoculated  with  a  pure  culture  of  the 
bacillus  of  anthrax.  Of  fifteen  animals  treated  in  this  way.  seven 
recovered,  while  all  the  control  animals  infected  with  anthrax,  but 
not  protected  by  the  microbe  of  erysipelas,  died  ;  of  the  seven 
animals  which  died  after  inoculation  of  both  microbes,  some  suc- 
cumbed to  the  anthrax  bacillus,  and  some  to  the  microbe  of  ery- 


ANTAGONISM    AMONG    MICKO -ORGANISMS.  69 

sipelas.  Therapeutic  inoculations  with  cultures  of  the  streptococ- 
cus erysipelatosus  in  animals  suffering  from  anthrax  were  not  as 
successful.  In  later  experiments  made  in  the  same  direction  in 
conjunction  with  Mattei,  it  was  ascertained  that  when  the  cocci  of 
erysipelas  were  injected  both  into  the  circulation  and  the  subcuta- 
neous tissues  of  rabbits  twenty-four  hours  before  the  infection  with 
anthrax,  the  bacilli,  even  when  administered  in  large  quantities, 
were  destroyed  in  from  twelve  to  seventeen  hours,  and  could  no 
longer  be  found  either  at  the  seat  of  infection  or  in  the  blood  and 
internal  organs,  whether  by  microscopical  examination,  or  by  cul- 
tivation experiments. 

Neumann  ("  Ueber  den  Einfluss  des  Erysipelas  auf  den  Yerlauf 
der  coustitutionellen  Syphilis/7  Allg.    Wiener  med.  Zeitung,  1888, 
No.  4)  communicates  two  observations  of  his  own  in  which  erysipe- 
las exerted  a  decided  beneficial  effect  on  syphilis. 

The  first  patient  was  a  woman,  fifty-six  years  old,  who  Avithin 
two  and  a  half  mouths  passed  through  three  attacks  of  facial  ery- 
sipelas, during  which  the  cutaneous  gummata  in  that  part  of  the 
face  affected  with  erysipelas  disappeared  completely.  The  second 
case  was  a  man,  twenty-six  years  old,  who  contracted  a  hard  chan- 
cre six  weeks  before  he  was  attacked  by  facial  erysipelas.  During 
the  acute  attack  the  primary  sore  improved  and  the  secondary 
symptoms  did  not  appear  until  seventy-three  days  after  the  infec- 
tion, and  then  in  only  a  mild  form,  so  that  the  erysipelas  had  the 
effect  of  postponing  the  secondary  symptoms. 

The  experimental  work  of  Watson  Cheyne  (London  Medical 
Record,  1887)  on  the  antagonistic  action  of  the  streptococcus 
erysipelatosus  upon  the  bacillus  of  anthrax  is  of  the  greatest  prac- 
tical and  scientific  importance.  He  experimented  on  rabbits ;  (a) 
by  inoculating  them  with  the  microbes  of  erysipelas,  and  two  to 
fourteen  days  later  with  anthrax  ;  (6)  by  simultaneous  intravenous, 
or  subcutaneous  inoculation  of  both  ;  (c)  by  inoculating  the  virus 
of  erysipelas,  after  anthrax  had  been  artificially  produced.  Of  the 
first  series  of  fifteen  animals,  seven  recovered,  while  all  the  control 
animals  died.  Of  the  second  series  of  sixteen  animals,  only  two 
recovered.  In  these  sets  of  experiments,  by  injection  of  a  half 
million  of  anthrax  bacilli,  all  the  control  animals  died,  whilst  all 
those  that  received  intravenous  injection  of  a  pure  culture  of  the 
microbes  of  erysipelas,  though  they  were  never  ill,  recovered. 

Schwimmer  ("Ueber  den  Heilwerth  des  Erysipels  bei  verschie- 
denen  Krankheitsformen,"  Wiener  med.  Presse,  1888,  Nos.  14,  15, 
16)  has  studied  with  special  care  the  antagonistic  properties  of  the 
streptococcus  of  erysipelas  in  different  infectious  diseases.  In 
syphilis,  the  lesions  occurring  in  the  erysipelatous  area  healed  more 
promptly.  In  a  case  of  obstinate  orchitis  and  epididymitis,  on  both 


70  ANTAGONISM    AMONG    MICRO-ORGANISMS. 

sides,  absorption  took  place  during  an  attack  of  facial  erysipelas ; 
no  material  improvement  was  observed  except  that  in  one  case  an 
ulcer  healed  more  rapidly.  The  author  saw  tubercular  glands  in 
the  neck  disappear  during  attacks  of  erysipelas  of  the  face  and  neck. 

Bruns  (Beitrdye  zur  klin.  Chirurgie,  B.  iii.  Heft  3)  has  collected 
twenty-two  cases  of  malignant  tumors  including  one  of  his  own,  of 
melano-sarcorna  of  the  breast,  in  which  a  final  cure  followed  an 
attack  of  erysipelas.  Out  of  5  sarcomata,  3  were  permanently 
cured,  while  the  other  2  were  diminished  in  size,  but  soon 
returned  to  their  former  size.  The  effect  of  the  erysipelatous 
invasion  proved  negative  in  6  cases,  in  which  the  diagnosis  between 
carcinoma  and  sarcoma  could  not  be  positively  made,  as  also  in  3 
cases  of  ulcerative  epithelioma.  It  is  stated  that  in  cicatricial 
keloid  and  lymphomata  the  attack  of  erysipelas  proved  curative. 

Garre  ("  Ueber  Antagonisten  unter  den  Backterien,"  Correspond 
denzblattf.  Schweizeraerzte,  B.  x.)  has  studied  the  antagonisms  among 
bacteria  on  artificial  culture-soils.  He  has  made  many  careful  ex- 
periments to  determine  the  growth  of  a  culture  of  germs  on  differ- 
ent nutrient  media  by  removal  of  the  entire  culture  with  a  minute 
spade,  and  inoculation  of  the  same  soil  with  another  microbe. 
From  the  results  thus  far  obtained,  he  has  ascertained  that  some 
microbes  affect  the  soil  favorably  for  the  growth  of  other  varieties, 
while  others  render  it  sterile.  For  example,  a  culture-medium 
impregnated  with  the  ptomaines  of  the  bacillus  fluorescens  putridus 
remains  perfectly  sterile  when  inoculated  with  pus-microbes. 
These  investigations  have  an  important  practical  bearing,  as  future 
research  may  not  only  show  the  way  to  secure  immunity  from 
infection  by  pathogenic  microbes  by  prophylactic  inoculations  with 
harmless  microbes,  but  may  likewise  establish  a  system  of  rational 
treatment  by  inoculations  of  cultures  of  antagonistic  bacteria  for 
therapeutic  purposes. 


CHAPTER   VII. 

INFLAMMATION. 

OUR  ideas  of  the  nature  of  inflammation  have  been  materially 
changed  by  the  knowledge  we  have  obtained  from  bacteriological 
investigations  which  have  been  made  during  the  last  fifteen  years. 
Inflammation  is  no  longer  viewed  as  a  disease.  Many  heretofore 
obscure  inflammatory  lesions  are  now  known  to  have  been  caused 
by  definite,  specific  microbes.  Modern  pathology  has  established 
the  fact  that  the  condition  called  inflammation  is  a  restorative  pro- 
cess, which  has  for  its  object  the  repair  of  injured  tissues,  or  the 
neutralization  or  removal  of  the  primary  microbic  cause.  From  a 
scientific  and  practical  standpoint,  all  inflammatory  affections  can  be 
divided  into  two  classes:  1.  Simple,  or  plastic  inflammation.  2. 
Infective,  or  destructive  inflammation. 

1.  Simple  or  Plastic  Inflammation. 

A  simple,  or  plastic,  inflammation  is  a  regenerative  process, 
induced  by  a  trauma,  or  disease,  in  which  the  tissues  are  in  an 
aseptic  condition,  and  the  products  of  tissue-proliferation  are  trans- 
formed into  normal  permanent  tissue.  During  the  first  stage  of 
inflammation  the  tissues  are  weakened,  so  that  they  cannot  resist 
in  any  way  the  entrance  of  pathogenic  microorganisms,  should  any 
reach  the  tissues  by  direct  contact,  or  through  the  circulation.  In 
the  second  stage,  the  weak  tissue  has  become  removed,  and  its  place 
is  occupied  by  vigorous  granulation  tissues,  which  possess  great 
power  in  resisting  the  attack  of  microbes.  In  the  third  stage,  the 
granulation  tissue  is  becoming  converted  into  mature  active  tissue, 
Prolonged  vascular  engorgement  and  the.first  stage  of  inflammation 
frequently  furnish  the  conditions  which  determine  transformation 
of  a  simple  into  a  septic  inflammation.  This  is  frequently  observed 
in  cases  of  acute  intestinal  obstruction,  in  which  the  vascular 
engorgement  and  incipient  inflammation  of  the  intestinal  tunics  so 
alter  the  tissues  of  the  bowel  that  pathogenic  microbes  pass  from 
the  intestinal  canal  into  the  peritoneal  cavity,  where  they  set 
up  a  septic  inflammation.  As  long  as  no  septic  infection  takes 
place  the  new  embryonal  cells  undergo  transformation  into  tissues 
which  correspond  to  the  anatomical  seat  of  the  lesion.  As  no  toxic 


72  INFLAMMATION. 

ptomaines  are  formed  in  simple  inflammation,  sepsis  and  febrile 
disturbances  are  either  absent  entirely  or,  when  present  in  a  slight 
degree,  are  caused  by  the  absorption  from  the  tissues  of  the  products 
of  tissue- wear,  or  the  introduction  of  fibrin  ferments  derived  from 
extra vasated  blood.  It  is  only  a  matter  of  time  until  the  process 
still  known  as  simple  inflammation  will  be  no  longer  considered 
and  classified  with  inflammatory  processes,  but  will  be  assigned  a 
separate  place  in  pathology,  as  it  resembles  in  every  respect  the 
physiological  processes  as  we  observe  them  during  the  growth  and 
regeneration  of  the  body. 

2.  Infective  Inflammation. 

The  characteristic  features  of  this  form  of  inflammation  are,  that 
it  is  caused  by  the  presence  of  specific  microbes,  and  that  the  pro- 
ducts of  the  inflammatory  process  do  not  undergo  transformation 
into  tissue  of  a  higher  type. 

Thoma  ("  Ueber  die  Ehitziindung,"  Berl.  klin.  Wochenschrift, 
Nos.  6,  7)  regards  suppuration  as  a  qualitative  alteration  of  inflam- 
mation. He  defines  it  as  an  exudation  plus  fermentation,  in  which 
the  latter  is  not  essentially  caused  by  microorganisms,  as  it  may  also 
be  caused  by  the  tissues,  as  they  also  are  known  to  possess  zymotic 
properties.  Caseation  is  also  looked  upon  as  the  result  of  fermen- 
tation, but  not  in  the  sense  described  by  Weigert,  but  more  allied 
to  digestive  and  putrefactive  processes. 

The  new  tissue  is  destroyed  either  rapidly  or  slowly,  by  the 
action  of  the  ptomaines ;  the  cells  undergo  retrograde  metamorpho- 
sis, and  are  absorbed  after  the  primary  cause  has  ceased  to  act,  or 
they  are  so  rapidly  destroyed  that  their  interstitial  removal  is  no 
longer  possible  and  the  product  of  the  inflammation  is  removed 
spontaneously,  or  by  the  intervention  of  art,  or,  finally,  life  is 
destroyed,  either  by  disturbances  due  to  mechanical  causes  or  by 
ptomaine-intoxication.  The  intensity  of  the  inflammation  depends 
as  well  upon  the  nature  of  the  microbes  as  their  quantity.  The 
microbes  of  suppuration,  gonorrhoea,  and  erysipelas  always  cause 
an  acute  inflammation,  while  tubercular  processes  and  allied  affec- 
tions are  noted  for  their  chronicity.  Glanders  and  actinomycosis 
are  chronic  or  subacute  affections.  In  the  same  organ,  the  primary 
seat  of  the  inflammatory  process  will  be  modified  by  the  kind  of 
microbe  which  has  caused  the  infection.  Thus,  in  suppurative  mas- 
titis, the  abscesses  which  are  caused  by  the  staphylococci  always 
begin  in  the  deeper  part  of  the  organ,  and  spread  toward  the 
surface,  while  in  infection  with  streptococci  of  the  same  part,  the 
inflammation  starts  from  some  superficial  abrasion  and  first  attacks 
the  skin,  whence  the  process  extends  in  a  central  direction  to  the 


INFECTIVE    INFLAMMATION.  73 

deeper  portions  of  the  gland,  where  suppuration  takes  place 
(Cheyne).  This  difference  depends  on  the  manner  of  invasion  of 
the  two  microbes.  The  staphylococci  enter  the  organism  through 
the  milk  ducts,  and  act  from  their  interior,  whereas  the  streptococci, 
like  the  streptococcus  of  erysipelas,  enter  the  tissues  through  the 
lymphatic  vessels,  and  their  pathogenic  action  is  primarily  observed 
at  the  surface.  Bumm  excised  a  portion  of  the  wall  of  a  commenc- 
ing abscess  of  the  breast,  and  was  able  to  demonstrate  the  presence 
of  staphylococci  in  the  interior  of  the  acini,  and  their  penetration 
thence  into  the  interacinous  tissue.  The  phlegmonous  inflamma- 
tion of  the  breast  caused  by  the  streptococci  takes  place  along  the 
.course  of  the  lymphatics,  and  primarily  involves  the  interacinous 
connective  tissue. 

During  the  first  stage  of  microbic  inflammation,  the  increased 
afflux  of  blood  may  be  looked  upon  as  an  attempt  to  wash  away 
the  microbes.  The  increased  velocity  of  the  blood-current  is  well 
calculated  to  prevent  mural  implantation  of  the  microbes,  and  to 
detach  such  as  have  become  fastened  upon  the  vessel  wall.  The 
next  attempt  on  the  part  of  the  tissues  is  to  limit  infection  by  the 
production  of  granulation  tissue.  The  tissues  which  first  come  in 
contact  with  the  primary  cause  of  the  inflammation  are  converted 
into  embryonal  tissue,  which  forms  a  wall  of  protection  for  the 
surrounding  tissues  around  the  primary  area  of  infection.  In  acute 
suppuration  this  granulation  tissue  is  transformed  into  pus,  and  the 
process  extends  until  limitation  takes  place  by  the  primary  cause 
becoming  less  virulent,  when  the  abscess  wall,  composed  of  living 
granulation  tissue,  forms  a  boundary-line  to  the  suppurative  pro- 
cess. In  chronic  infective  processes,  as  tuberculosis  and  actinomy- 
cosis,  the  granulating  stage  remains  for  an  indefinite  period  of  time, 
and  in  the  former  affection,  under  favorable  conditions,  retrograde 
degenerative  changes  are  prevented,  the  embryonal  cells  are  trans- 
formed into  connective  tissue,  and  a  spontaneous  cure  is  the  result. 
During  the  third  stage  the  microbes  have  either  been  removed  or, 
at  least,  their  pathogenic  properties  no  longer  exist,  and  a  process 
of  repair  is  initiated.  It  has  been  shown  experimentally  that 
microbes  enter  the  organism  most  rapidly  during  the  first  stage  of 
inflammation,  as  studied  in  tissues  the  seat  of  a  simple  inflamma- 
tion produced  by  the  action  of  chemical  irritants,  and  subsequently 
infected  by  the  introduction  of  pathogenic  microbes.  It  has  been 
found,  as  regards  pus-microbes,  that  if  they  are  circulating  in  the 
blood,  the  induction  of  a  severe  inflammatory  action  does  not  lead 
to  their  localization  in  the  part,  while  if  the  inflammation  is  chronic, 
or  the  trauma  less  intense,  they  become  arrested  in  the  inflamma- 
tory depot  and  set  up  suppuration.  Thus,  Rhine  concluded  from 
his  experiments  on  suppuration,  quoted  elsewhere,  that  a  violent 


74  INFLAMMATION. 

inflammatory  action  did  not  produce  a  locus  minoris  resistentice,  but 
that  the  slightest  injury  caused  by  the  chemical  products  of  the  bac- 
teria themselves  sufficiently  weakened  the  part  to  enable  the  organ- 
isms to  grow  in  it.  Acute  osteomyelitis  and  local  tuberculosis 
follow  not  severe,  but,  as  practical  experience  has  shown,  trifling 
injuries.  In  phthisical  patients  a  severe  wound  or  fracture  is  not 
followed  by  local  tuberculosis,  but  slight  injuries  determine  locali- 
zation. Chronic  infective  inflammations,  as  tuberculosis,  syphilis, 
and  actinomycosis,  often  lay  the  foundation  for  acute  supptirative 
inflammation,  as  the  foci  of  granulation  tissue  determine  localiza- 
tion of  floating  pus-microbes,  and  the  embryonal  tissue  furnishes 
the  most  favorable  local  conditions  for  their  pathogenic  action. 
Acute  septic  peritonitis  has  been  made  the  subject  of  careful  experi- 
mentation with  special  reference  to  its  etiology. 

Pawlowsky  (Beitrage  zur  Aetiologie  und  Entstehuugsweise  der 
akuten  Peritonitis/7  Centmlblatt  f.  Chirurgie,  1887,  No.  48)  made 
10  series,  with  101  experiments.  The  chemical  irritants,  or  cul- 
tures, were  introduced  through  the  canula  of  a  small  trocar  under 
strict  antiseptic  precautions,  and  the  small  wound  carefully  closed 
with  iodoform  collodium.  The  first  series  consisted  of  experi- 
ments with  croton  oil  on  three  dogs  and  nine  rabbits.  The  amount 
of  croton  oil  injected  varied  from  six  drops  to  one-tenth  of  a 
drop.  The  smallest  doses  produced  no  symptoms.  Large  doses 
produced  a  severe,  acute  hemorrhagic  peritonitis,  the  intensity  of 
which  was  proportionate  to  the  amount  of  the  irritant  injected. 
The  peritoneal  effusion,  under  the  microscope,  was  seen  to  contain 
red  and  white  blood-corpuscles.  Inoculations  of  different  nutrient 
media  with  the  fluid  yielded  negative  results.  In  the  next  series 
of  experiments,  an  aqueous  solution  of  trypsin  and  pancreatin 
was  injected  for  the  purpose  of  determining  whether  the  diges- 
tive ferments  in  the  event  of  intestinal  perforation  could  produce 
peritonitis.  The  experiments  established  that  trypsiu  acts  as  a 
powerful  irritant  upon  the  peritoneum.  Injection  of  one-half 
gramme  of  trypsin  dissolved  in  sterilized  water  caused  in  rabbits  a 
severe  hemorrhagic  peritonitis,  with  a  copious  exudation  and  death 
in  from  four  to  four  and  one-half  hours.  In  doses  of  from  one- 
fourth  to  one-tenth  of  a  gramme  hemorrhagic  peritonitis  was  also 
produced,  but  death  did  not  occur  until  twenty  to  twenty-four  hours 
after  the  injection.  One-twentieth  of  a  gramme  produced  no  symp- 
toms. Nutrient  media  inoculated  with  the  products  of  inflamma- 
tion remained  sterile.  Next,  the  peritoneal  cavity  was  infected 
with  plate  cultures  of  different  microbes  suspended  in  sterilized 
water.  The  first  experiments  were  made  with  non-pathogenic 
germs.  Four  rabbits  and  one  dog  were  injected  with  large  quanti- 
ties of  a  micrococcus  which  was  obtained  from  a  plate  culture 


INFECTIVE    INFLAMMATION.  75 

inoculated  with  pus  ;  the  micrococcus  was  exactly  similar  to  the 
staphylococcus  albus,  for  which  it  was  first  mistaken  ;  later,  it  was 
shown  that  it  was  not  a  pus-microbe,  as  it  did  not  liquefy  gelatin. 
All  of  the  animals  recovered.  Two  rabbits  inoculated  with  an 
entire  culture  of  yellow  sarcinse  upon  agar,  mixed  with  one-tenth  of 
a  drop  of  croton  oil,  also  recovered.  The  experiments  with  patho- 
genic microbes  always  produced  positive  results.  Three  series, 
with  three  separate  microorganisms,  were  carried  out.  The  staphy- 
lococcus pyogeues  aureus  grown  from  osteomyelitic  pus  was  first 
used.  In  seventeen  out  of  forty-one  experiments,  this  microbe 
alone  was  used ;  in  eleven  it  was  mixed  with  croton  oil,  in  six  with 
trypsin,  and  in  seven  with  agar-agar.  From  injections  with  the 
staphylococcus  alone,  the  following  results  were  obtained  : 

1.  Large  quantities  produced  fibrinous  suppurative  peritonitis. 

2.  In  quantities  of  two  plate  cultures,  four  rabbits  succumbed 
to  suppurative  peritonitis. 

3.  Half  of  this  quantity  produced  the  same  results. 

4.  In  yet  smaller  quantities,  still  the  same  result,  and  peritonitis 
only  failed  to  develop  when  a  very  minute  quantity  of  the  culture 
was  used.  • 

In  all  cases  in  which  peritonitis  was  produced,  inoculations  of 
the  products  of  inflammation  upon  nutrient  media  yielded  positive 
results.  In  hardened  specimens  of  the  peritoneum,  stained  with 
various  coloring  agents,  the  microorganisms  could  be  seen  in  the 
lymph  spaces.  The  suppurative  nature  of  the  peritonitis  thus 
induced  became  more  apparent  the  longer  life  was  prolonged.  An 
entire  agar  culture  of  the  bacillus  pyocyaneus  caused  death  in  from 
twenty-four  to  forty-eight  hours.  The  autopsy  revealed  a  fibriuous 
hemorrhagic  peritonitis.  The  exudation  consisted  largely  of  red 
corpuscles  and  a  large  unmber  of  bacilli.  Pure  cultures  of  the 
bacillus  could  be  obtained  by  inoculating  the  fluid  upon  agar-agar. 
One-fifth  of  this  quantity  proved  harmless. 

M  «jln  hardened  sections,  the  bacilli  were  found  in  the  lymph  spaces 
of  the  central  tendon  of  the  diaphragm,  the  parietal  peritoneum, 
visceral  peritoneum,  and  in  the  capsule  of  the  spleen  and  liver,  also 
in  the  uriniferous  tubules  and  Malpighian  bodies  of  the  kidney. 
The  next  series  of  experiments  was  made  to  ascertain  what  caused 
the  inflammation  in  cases  of  perforative  peritonitis.  The  fresh 
intestinal  contents  of  a  healthy  animal,  just  killed,  were  divided 
into  three  parts,  one  of  which  was  at  once  injected  into  several 
rabbits  without  filtration,  in  doses  of  one  syringefnl.  The  second 
portion  was  filtered,  and  of  the  filtrate  two  and  a  half  to  three  and 
a  half  syriugefuls  were  injected  into  each  rabbit;  the  third  portion 
was  sterilized  according  to  Tyndall's  directions  for  eight  days,  and 
then  one  syringeful  was  injected  into  each  animal.  The  results 


76  INFLAMMATION. 

were  as  follows  :  Four  rabbits  died  of  fibrinous  suppurative  perito- 
nitis from  the  injection  with  the  first  portion.  Four  rabbits  injected 
with  the  filtered  feces,  recovered,  as  did  one  rabbit  inoculated  with 
the  sterilized  portion.  At  the  autopsy,  particles  of  the  intestinal 
contents  were  found  in  the  peritoneal  cavity  covered  with  fibrin, 
and  microscopically  peculiar,  short  bacilli.  This  microbe  he  called 
bacillus  peritonitidus  ex-intestinalis  cuniculi,  and  describes  the  cul- 
tures upon  agar-agar  plates  as  shining,  grayish-white,  oil  paint-like 
colonies.  It  does  not  liquefy  gelatin.  The  bacillus  is  non- motile. 
With  cultures  of  this  bacillus  he  made  nine  experiments  on  rabbits 
and  two  on  dogs.  Each  animal,  which  received  an  entire  agar 
culture,  died  of  hemorrhagic  peritonitis  in  from  twenty  to  twenty- 
four  hours.  Smaller  quantities  produced  death  from  the  same 
cause  in  from  twenty-four  to  seventy-two  hours.  Still  smaller 
doses  produced  a  suppurative  peritonitis,  and  death  after  a  number 
of  days.  Of  the  two  dogs,  each  injected  with  an  agar  culture,  one 
died  after  twenty-four  hours  of  incipient  hemorrhagic  peritonitis, 
the  other  recovered  after  an  illness  of  several  days'  duration.  In 
the  fatal  cases,  the  bacilli  were  found  in  different  internal  organs, 
and  could  again  be  reproduced  by  inoculations  with  the  infected 
tissues  upon  nutrient  media.  He  believes  that  this  bacillus  is  the 
essential  cause  of  perforative  peritonitis.  He  also  asserts  that  the 
fibriuous  form  of  peritonitis  is  the  least  dangerous,  as  the  layers  of 
fibrin  tend  to  limit  the  ingress  of  microbes  into  the  organism. 
The  fibrinous  purulent  variety  is  the  next  formidable  form,  while 
in  the  most  rapidly  fatal  cases  of  septic  peritonitis  the  local  lesion 
is  not  characterized  by  any  macroscopical  tissue-changes. 

Alexander  Frankel  (Wiener  Mm.  Woehenschrif  1,1888,^0$.  30- 
32)  testifies  to  the  harmlessness  of  pure  cultures  of  microbes  when 
injected  into  the  peritoneal  cavity  of  rabbits.  Fehleisen  (Arddv 
/.  Idin.  Chirurgie,  B.  xxxvi.  p.  978)  injected  pus  from  abscesses 
containing  the  staphylococcus  pyogenes  aureus  in  doses  of  from  4 
to  8  c.cm.  into  the  peritoneal  cavity  of  rabbits  without  producing 
peritonitis  in  every  instance,  or  even  as  a  rule,  although  in  some 
instances  the  animals  died  from  injection  of  a  much  smaller  quan- 
tity. Fehleisen  is  of  the  opinion  that  the  number  of  microbes  in 
the  pus  does  not  determine  its  virulence. 

Orth  ("  Experimentelles  iiber  Peritonitis,"  Berl.  klin.  Woohen- 
schrift,  October  28,  1889)  agrees  with  Grawitz  that  when  a  pure 
culture  of  pus-microbes  is  injected  into  a  healthy  peritoneal  cavity 
no  suppuration  is  produced.  But  his  experiments  proved  what  is 
of  the  greatest  practical  interest,  that  if  the  peritoneum  is  wounded 
under  antiseptic  precautions  peritonitis  is  invariably  produced,  if 
somewhere  else  in  the  body  suppuration  existed  at  the  same  time. 
If,  for  instance,  an  abscess  in  the  subcutaneous  tissue  was  produced, 


INFECTIVE    INFLAMMATION.  77 

and  then  the  intestine  was  temporarily  rendered  impermeable,  the 
animal  died  without  exception  of  peritonitis.  The  same  result  fol- 
lowed if  the  pus-microbes  were  injected  directly  into  the  circula- 
tion, but  not  if  they  were  introduced  through  the  alimentary  canal. 

Laruelle  ("Etude  bacteriologique  sur  les  peritonites  par  perfora- 
tion," La  Cellule,  T.  V.  Louvaiu,  1889)  produced  peritonitis  artifi- 
cially in  dogs  and  rabbits,  and  from  his  observations  came  to  the 
conclusion  that  the  localization  of  pus-microbes  in  the  peritoneal 
cavity  is  greatly  favored  by  the  action  of  chemical  substances. 
He  believes  that  peritonitis  is  not  produced  by  the  specific  microbe 
described  by  Pawlowski.  He  claims  that  the  microorganism  dis- 
covered by  Pawlowski  is  the  bacillus  coli  communis. 

Weichselbaum  ("  Der  Diplococcus  pneumonia  als  Ursache  der 
primaren,  akuten  Peritonitis,'7  Centralblatt  /.  Bakteriologie,  B.  v. 
No.  2)  found  in  three  cases  of  acute  peritonitis  the  diplococcus  of 
pneumonia  and  no  pus-microbes.  In  one  case  the  peritonitis  was 
complicated  with  pneumonia,  in  the  second  case  it  was  followed  by 
double  pleuritis,  and  in  the  third  case  the  disease  was  doubtless 
primary. 

Wegner  (Archiv  f.  klin.  Chirurgie,  1877)  has  shown  by  his  ex- 
periments that  a  great  variety  of  fluids  free  from  septic  germs, 
such  as  water,  bile,  urine,  blood,  etc.,  can  be  injected  into  the  peri- 
toneal cavity  of  rabbits  without  any  serious  results  following. 
Even  large  quantities  of  unfiltered  air  proved  innocuous  when  in- 
troduced in  the  same  manner.  Putrescible  fluids  when  injected  in 
small  quantities  were  rapidly  absorbed  without  producing  perito- 
nitis, but  when  the  quantity  injected  was  large  and  insufflation  of 
air,  unfiltered,  was  practised  at  the  same  time,  putrefaction  and 
death  from  septic  intoxication  occurred. 

Grawitz  (Virchow's  Archiv,  B.  cviii.)  proved  that  saprophytic 
bacteria,  when  injected  into  a  normal  peritoneal  cavity,  were 
promptly  destroyed  and  absorbed.  In  cases  in  which  the  injection 
was  made  into  a  peritoneal  cavity  which  had  previously  undergone 
alterations  by  injury  or  disease,  or  in  which  the  quantity  of  fluid 
was  too  great  for  rapid  absorption,  symptoms  of  intoxication,  as 
described  by  Wegner,  resulted,  but  these  symptoms  were  unaccom- 
panied by  suppurative  peritonitis.  A  healthy  peritoneal  cavity 
has  also  been  found  capable  of  disposing  of  a  limited  quantity  of 
pure  cultivations  of  pus-microbes,  the  germs  being  removed  by 
absorption  and  destroyed  in  the  circulation.  Bnt  when  pyogeuic 
organisms  are  introduced  into  an  abdominal  cavity,  where  the 
absorptive  powers  of  the  peritoneum  have  been  diminished  or  sus- 
pended by  antecedent  pathological  conditions,  suppurative  perito- 
nitis is  the  usual  result.  When  pus-microbes  are  introduced  in 
large  quantities,  even  into  a  healthy  peritoneal  cavity,  the  pre- 


78  INFLAMMATION. 

formed  ptomaines,  by  their  chemical  actions,  so  alter  the  tissues 
that  the  process  of  absorption  is  impaired,  and  suppurative  perito- 
nitis again  results  in  consequence.  The  greatest  clinical  difference 
between  simple  peritonitis  produced  by  a  trauma  or  chemical  irri- 
tants, and  septic  peritonitis,  consists  in  the  course  and  extent  of 
the  inflammation.  Simple  inflammation  produced  by  aseptic  causes 
remains  limited  to  the  seat  of  the  trauma,  and  does  not  extend  much 
beyond  the  surface  area  to  which  the  irritant  is  applied  ;  while 
septic  peritonitis  is  always  characterized  by  its  progressive  charac- 
ter, as  the  cause  upon  which  it  depends  is  multiplied  within  the 
peritoneal  cavity.  The  same  can  be  said  of  the  two  kinds  of 
inflammation  in  any  other  tissue  or  part  of  the  body.  The  same 
conditions  which  were  found  to  favor  the  development  of  septic 
peritonitis,  such  as  trauma  and  the  presence  of  fluids,  are  equally 
potent  in  determining  localization  of  microbes  in  other  parts  of  the 
body,  and  intensify  their  pathogenic  action  by  creating  conditions 
which  prevent  their  absorption  and  destruction,  and,  on  the  other 
hand,  they  furnish  a  nutrient  medium  in  which  the  microbes  find 
a  proper  soil  for  their  multiplication. 

Kinne  (u  Der  Eiteruugs  process  und  seine  Metastaseu,"  Archiv  f. 
klin.  Chirurgie,  B.  xxxix  p.  13)  is  of  the  opinion  that  on  account 
of  the  rapidity  with  which  absorption  takes  place  in  the  peritoneal 
cavity  that  the  peritoneum,  when  in  a  normal  condition,  is  almost 
immune  to  infection  with  pus-microbes.  He  injected  from  30  to  35 
c.c.  of  an  aqueous  suspension  of  a  pure  culture  of  pus-microbes  into 
the  peritoneal  cavity  of  healthy  animals,  and  was  never  able  in  this 
manner  to  produce  a  peritonitis.  He  had  no  better  success  with 
injections  of  a  mixture  of  a  gelatin  culture  of  staphylococcus  aureus 
and  a  turbid  culture  of  the  same  coccus  in  bouillon.  He  also  injected 
from  day  to  day  a  boiled  putrid  solution  to  which  was  added  a 
culture  of  the  staphylococcus  aureus  without  any  inflammation  fol- 
lowing. The  experiments,  as  a  rule,  were  made  on  dogs,  although 
in  several  instances  rabbits,  guinea-pigs,  and  white  rats  were  used. 
He  believes  that  the  difference  in  the  results  obtained  by  him  and 
Grawitz,  as  compared  with  Pawlowski's,  consist  in  the  nature  of 
the  abdominal  wound.  Pawlowski  made  an  incision  down  to  the 
muscles  and  then  perforated  the  abdominal  wall  with  a  blunt  tro- 
car, while  he  and  Grawitz  used  a  sharp,  hollow  needle  for  making 
the  injection.  To  prove  that  his  injections  entered  the  peritoneal 
cavity  he  added  coal-dust,  which  he  found  in  the  peritoneal  cavity 
in  making,  subsequently,  the  autopsy. 


CHAPTEE    VIII. 

SUPPURATION. 

THE  wonderful  results  which  were  obtained  by  the  antiseptic 
treatment  of  wounds  made  it  exceedingly  probable  that  all  wound- 
infective  diseases  were  caused  by  living  microorganisms.  The 
probability  was  increased  when  Koch,  in  1879,  showed  the  direct 
connection  existing  between  certain  traumatic  infective  diseases  in 
animals  and  the  never-absent  definite  microorganisms.  It  requires 
no  longer  any  arguments  to  show,  at  this  time,  that  all  wound- 
infective  diseases,  among  them  particularly  suppuration,  are,  with- 
out exception,  caused  by  the  introduction  into  the  tissues  of  the 
organism  of  specific  pathogenic  microbes.  This  part  of  the  work 
has  been  prepared  with  special  reference  to  the  etiology  of  acute 
suppuration,  as  chronic  suppuration  is  intimately  associated  with 
that  of  surgical  tuberculosis  and  other  forms  of  infective  diseases, 
which  usually  pursue  a  chronic  course,  and  differs  greatly  in  its 
pathology  from  the  other. 

Etiologically,  most  of  the  purulent  processes  constitute  more  of 
a  unity  than  was  formerly  believed,  and  the  clinical  varieties  are 
mostly  determined  by  the  intensity  of  the  infection  and  by  the 
manner  of  localization.  The  most  conclusive  evidence  of  the 
correctness  of  this  assertion  is  furnished  by  the  fact  that  the  same 
streptococcus  which  produces  a  simple  abscess  is  likewise  the  most 
frequent  cause  of  progressive  gangrene  and  of  that  most  grave 
form  of  suppuration — pyaemia. 

HISTORY. — As  in  the  case  of  nearly  all  infective  diseases,  years 
before  the  specific  microorganisms  of  suppuration  were  discovered, 
living  organisms  were  found  and  described  in  pus,  and  were  believed 
to  be  the  cause  of  the  suppuration.  In  1865,  Klebs  detected  in 
the  tubuli  uriniferi  in  cases  of  pyelo- nephritis  following  suppura- 
tive  cystitis,  between  the  pus-cells  small,  round  cocci,  which  he 
believed  produced  the  infection.  In  1872,  the  same  author  (Schuss- 
wuuden,  Leipzig,  1872)  published  the  result  of  his  researches 
during  the  Franco-Prussian  War  on  septic  wound  diseases.  In 
this  work  he  again  referred  to  the  organism  which  he  ha^  previ- 
ously described,  and  showed  that  it  existed  in  the  tissues  and 
organs  the  seat  of  suppurative  inflammation  before  pus  had  formed. 


80  SUPPURATION. 

He  also  showed  how  these  organisms  enter  the  circulation  and  are 
the  direct  cause  of  pathological  changes  in  distant  organs,  Even 
at  that  time  he  placed  great  stress  on  the  fact  that,  as  long  as  the 
cocci  remained  only  in  the  tissues  at  the  point  of  infection  they 
caused  only  local  inflammatory  conditions  or  necrosis,  but  as  soon 
as  they  entered  the  circulation  fever  and  other  symptoms  of  general 
septic  infection  followed. 

It  was  not  until  1881  that  Ogston  (u  Report  upon  Microorgan- 
isms in  Surgical  Diseases/7  British  Medical  Journal,  March,  1881, 
p.  369)  announced  his  great  discovery,  which  has  since  revolution- 
ized the  study  of  acute  suppuration.  This  patient  investigator 
examined  the  pus  of  69  abscesses  for  microorganisms,  and  found 
in  17  of  them  a  chain  coccus  (streptococcus),  in  31  cocci  which 
arranged  themselves  in  groups  which  resembled  a  bunch  of  grapes 
(staphylococcus),  and  in  16  both  of  these  forms  were  present.  In 
cold  abscesses  neither  of  these  microorganisms  was  found.  He  also 
found  that  these  two  forms  of  microbes  differed  in  their  action  on 
the  tissues,  as  the  streptococcus,  following  the  lymphatic  channels, 
was  seen  to  be  the  cause  of  diffuse  suppurative  processes,  while  the 
staphylococcus  was  found  only  in  abscesses  which  were  circum- 
scribed. Rosenbach  took  up  the  work  where  Ogston  left  it,  and, 
as  the  fruit  of  a  number  of  years  of  patient  study  and  research, 
published  his  classical  work  in  1884  (Microc rganismen  bei  den 
Wund -infections  Krankheiten  des  Menschen,  Wiesbaden,  1884). 
This  work  must  serve  as  a  basis  for  all  future  research  on  suppura- 
tive inflammation.  Rosenbach  availed  himself  of  the  advantages 
offered  by  an  improved  technique  in  bacteriological  research,  and 
cultivated  the  pus-microbes  upon  solid  nutrient  media,  and  pointed 
out  the  difference  in  macroscopical  appearances  of  the  cultures  of 
the  different  kinds  of  pus-microbes  which  enabled  him  to  differen- 
tiate between  them  by  the  naked-eye  appearances  of  the  cultures 
upon  the  nutrient  media.  He  discovered  the  staphylococcus  pyo- 
genes  aureus,  the  micrococcus  pyogenes  teuuis,  and  three  bacilli 
saprogenes. 

Passet  should  be  mentioned  next  after  Rosenbach,  in  the  long 
list  of  distinguished  men  who  have  made  the  etiology  of  suppu- 
ration a  special  study.  Passet  ("  Ueber  Microorganismen  der 
eitrigen  Zellgewebs-entzimdung  des  Menschen,"  Fortschritte  der 
Mediein,  1885,  Nos.  2,  3)  discovered  and  described  the  staphylo- 
coccus citreus,  cereus  albus  and  flavus,  and  from  a  peri-rectal 
abscess  he  cultivated  the  bacillus  pyogenes  foetidus.  The  strepto- 
coccus which  he  found,  he  claimed  was  different  from  the  one 
described  by  Rosenbach,  as  it  resembled  more  closely  the  strepto- 
coccus oT  erysipelas. 


DIFFERENT    KINDS    OF    PUS-MICROBES.  81 


Description  of  the  Different  Kinds  of  Pus-microbes. 

1.  STAPHYLOCOCCUS  PYOGENES   AUREUS  is   the  pus-microbe 
most  frequently  present  in  acute  abscesses.    Cocci  singly,  or  aggre- 
gated in  masses.     It  grows  readily  upon  gelatin,  agar-agar,  coagu- 
lated   blood-serum,    and    potato.      It   possesses    the   property    of 
liquefying  gelatin.     It  grows  readily  at  the  ordinary  temperature, 
but  more  rapidly  when  the  temperature  is  not  less  than  30°  C. 
(86°  F.),  and  does  not  exceed  that  of  the  normal  temperature  of 
the  body.     It  peptouizes  albumen  and  coagulates  milk.     The  cul- 
ture grows  in  the  track  of  the  needle  and  upon  the  surface  of  the 
nutrient  medium.     The  culture  presents  a  gold-yellow  appearance. 

Liibbert  ("  Biologische  Spaltpilzuntersuchung.  Der  Staphylo- 
coccus  pyogenes  aureus  und  der  Osteomyelitis-coccus."  Wiirz- 
burg,  1886)  has  made  an  extended  and  thorough  study  of  this 
microbe.  It  was  examined  in  reference  to  its  behavior  to  light, 
temperature,  and  the  various  culture  substances.  Kreatin  was 
found  to  be  its  simplest  nitrogenous  nutrient  material.  Carbonic 
acid  arrests  its  growth,  while  oxygen  not  only  favored  its  growth, 
but  also  accelerated  the  production  of  the  orange-yellow  pigment 
material  which  distinguishes  it  from  the  other  staphylococci.  Milk 
rendered  sour  by  the  addition  of  a  pure  culture  of  this  microbe, 
and  tested  with  the  salts  of  barium,  snowed  the  presence  of  methyl- 
alcohol,  lactic  and  butyric  acids.  It  was  ascertained  that  it  pro- 
duced carbonic  acid  and  absorbed  oxygen.  Corrosive  sublimate, 
1:81400,  and  thymol,  1:1100,  arrested  its  growth.  A  dried 
culture,  exposed  for  an  hour  to  a  temperature  of  86°  C.  (176°  F.), 
was  rendered  completely  sterile.  Its  pathogenic  properties  were 
found  greatest  in  cultures  made  directly  from  the  diseased  tissues, 
while  its  virulence  diminished  through  successive  cultures.  A  cul- 
ture, attenuated  in  this  manner,  again  regained  its  virulence  by 
being  passed  through  the  animal  body.  Large  quantities  of  this 
microbe  injected  into  the  subcutaneous  tissue  of  rabbits  produced 
a  general  infection,  the  kidneys  and  muscles  of  the  heart  being  the 
organs  first  attacked.  If  injected  into  the  knee-joint  of  a  dog  sup- 
puration occurred,  followed  by  disintegration  of  the  joint.  It  is 
identical  with  the  organism  which  has  been  described  in  acute 
osteomyelitis,  and  at  first  supposed  to  be  the  specific  organism  of 
that  disease. 

2.  STAPHYLOCOCCUS  PYOGENES  ALBUS. — Same  as  aureus,  but 
produces  no  pigment,     Both  Passet  and  Klebs  have  observed  in 
the  white  culture  of  this  coccus  small  yellow  dots,  which,  when 
isolated,  lost  their  color.     These  authors,  therefore,  consider  the 
yellow  and  white  staphylococcus  as  varieties  of  the  same  kind.     Its 
pathogenic  properties,  both  in  man  and  animals,  are  somewhat  less 

6 


82  SUPPURATION. 

intense  than  those  of  the  aureus.  The  cultures  of  both  the  yellow 
and  white  staphylococcus  upon  gelatine  present  an  irregular  sur- 
face, and  the  margins  are  dotted  with  numerous  minute  globular 
projections.  Both  of  these  microbes  liquefy  gelatin,  but  agar- 
agar  and  coagulated  blood-serum  are  not  similarly  affected.  The 
cultures,  especially  if  kept  moist,  retain  their  virulence  for  a  very 
long  time.  Rosenbach  found  a  culture  upon  serum  active  after 
the  lapse  of  two  years. 

3.  STAPHYLOCOCCUS   PYOGEXES    CITREUS. — Like  the  former, 
liquefies  gelatin.  '  Cocci  singly,  or  in  pairs,  or  zoogloea.     If  cul- 
tivated  on   nutrient   gelatin,  or  agar-agar,  a   sulphur  or  lemon- 
yellow  growth  develops  after  twenty-four  hours,  which,  at  that 
time,  resembles  the  aureus,  but  later  does  not  change  into  an  orange- 
yellow  color.     In   both,  the  development  of  pigment  only  takes 
place  where  the  colonies  are  in  contact  with  the  air.     According  to 
Passet,  its  pathogenic  properties  are  somewhat  less  than  those  of 
the  aureus  and  albus.     This  latter  statement  has  received  the  con- 
firmation of  Cheyne.     When  inoculated  under  the  skin  of  mice, 
guinea-pigs,  or  rabbits,  an  abscess  forms  after  a  few  days,  from 
which  a  fresh  culture  of  the  microbe  can  be  obtained. 

4.  STAPHYLOCOCCUS   CEREUS   ALBUS. — Cocci   also  obtainable 
from   pus,  but    distinguished  by   forming  on    nutrient   gelatin  a 
white,  slightly  shining  layer,  like  drops  of  white  wax,  with  some- 
what thickened,  irregular  edge      The   needle  puncture   develops 
into  a  grayish-white,  granular  thread.     In  plate  cultivations,  on 
the  first  day,  white  points  are  observed,  which  spread  themselves 
out  on  the  surface  to  spots  of  one-half  a  millimetre  in  diameter ; 
when  cultivated  on  blood-serum,  a  grayish-white,  slightly  shining 
streak  develops ;  and  on  potato  the  cocci  form  a  layer  which  is 
similarly  colored.     This  microbe  is  not  pathogenic  in  rabbits. 

5.  STAPHYLOCOCCUS  CEREUS  FLAVUS. — If  cultivated  on  gela- 
tin, the  growth,   which  is  at  first  white,  becomes  a  citron-yellow 
color,  somewhat  darker  than  staphylococcus  pyogenes  citreus.  Both 
varieties  of  staphylococcus  cereus  are  found  in  pus  and  cultures  in 
colonies.     Inoculations  in  rabbits  have  proved  harmless. 

6.  STAPHYLOCOCCUS  FLAVESCEXS. — This  organism  was  found 
in    an    abscess  by  Babes,  and   occupies  an  intermediate  position 
between   the   staphylococcus    aureus    and   albus.     On  gelatin,  the 
growth  forms  a  colorless  layer,  and  causes  liquefaction.     It  is  fatal 
to  mice,  sometimes  causing  abscesses,  and,  in  large  doses,  septi- 
caemia. 

7.  MICROCOCCUS   PYOGENES   TENUIS. — Roseubach  found   this 
microorganism   in   a  large  abscess  which   had  given    rise    to    no 
general    symptoms.     It   is   of  rare   occurrence.     On   agar-agar   it 
forms  an  exceedingly  delicate,  almost  invisible,  white  film.     The 


PLATE    I  I. 


Staphylococci.     (After  Rosenbach.)     962  diam. 

a.  From  a  culture  twenty-four  days  old. 

b.  From  a  culture  two  months  old. 


DIFFERENT    KINDS    OF    PUS-MICROBES.  83 

individual  cocci  are  irregular  in  shape,  and  larger  than  the  staphy- 
lococci.  In  all  cases  in  which  this  microbe  is  the  sole  cause  of  the 
suppuration,  the  process  appears  to  have  been  not  attended  by  any 
very  severe  inflammatory  symptoms,  and  little  or  no  general  febrile 
disturbances.  Rosenbach  made  no  experiments  to  test  its  patho- 
genic properties  in  animals. 

This  microbe  was  never  found  by  anyone  else  but  Rosenbach 
until  February,  1888,  when  Raskina  (Transactions  of  Russian 
Medical  Association,  1889,  p.  327)  isolated  it  from  the  pus  and 
organs  in  a  case  of  scarlatina  complicated  with  pyaemia,  which 
proved  fatal  on  the  eighteenth  day  of  the  commencement  of  the 
primary  disease.  At  the  necropsy  multiple  miliary  abscesses  were 
found  in  the  kidneys  at  the  junction  of  cortex  and  medullary  por- 
tion. From  these  the  micrococcus  pyogeues  tennis  was  obtained 
in  a  state  of  pure  cultivation,  and  from  the  parenchymatous  portion 
of  the  kidney  a  diplococcus  of  unknown  species  was  cultivated. 
Inoculations  of  rabbits  with  a  pure  culture  of  the  micrococcus 
gave  negative  results,  even  though  the  coccus  was  present  in  the 
blood  twenty-four  hours  after  inoculation,  hence  it  is  problematical 
as  to  its  being  a  pyogenic  microbe.  Like  the  staphylococcus 
cereus,  it  probably  belongs  to  the  so-called  metabiotic  microbes  of 
Garre,  occurring  secondarily  after  suppuration  has  been  established 
by  genuine  pyogenic  microbes. 

8.  STREPTOCOCCUS  PYOGENES. — Cocci  singly,  or  arranged   in 
chains  often  of  great  length,  Fig.  2  (Roseubach).     Cultures  grow 
very  slowly  on  ordinary  nutrient  media  at 
the   summer   temperature,  but  with    greater 
rapidity   at   the    temperature   of   the   body.  OH 

Cultivated  in  a  streak  on  the  surface  of  gela-  r'V**?*'  w 
tin  on  a  glass  plate,  this  microbe  forms  at  /!,,:•.  ^  \ 
first  whitish,  somewhat  transparent  rounded  /^  V 

spots,  of  the  size  of  small  grains  of  sand.    On 
nutrient  agar-agar  it  grows  most  energetically  £ 

at  a  temperature  of  35°-37°  C.  (95c-98.6°  V,f ' 

F.).     Even  if  the  inoculation  is  made  with 

'        ni  .  ,.  ,  ,  Streptococcus  pyo2;enes. 

a    needle  in   a  continuous    line,    the  culture  (ROSENBACH) 

appears  in  small  dots.     In  its  further  growth, 

the  culture  is  elevated  in  the  centre,  and  presents  a  pale  brownish 
color,  while  the  periphery  is  flattened,  except  at  the  extreme  margin, 
which  is  again  raised,  and  often  with  a  spotted  appearance.  Still 
later,  the  periphery  develops  successive  layers  or  terraces.  The 
growth  is  so  slow  that  in  two  or  three  weeks  the  maximum  width 
of  the  culture-streak  is  about  two  or  three  millimetres.  In  a 
vacuum,  peptonizatiou  of  albumen  and  beef  takes  place  rapidly. 
In  the  subcutaneous  tissue  of  rabbits  in  small  quantities  they  cause 


84  SUPPURATION. 

a  transient  redness ;  when  larger  quantities  are  used  some  authors 
claim  they  produce  small  circumscribed  abscesses.  If  a  pure  cul- 
ture is  injected  into  a  serous  cavity,  it  causes,  first,  inflammation, 
and,  later,  effusion,  which  is  again  absorbed. 

9.  BACILLUS  PYOGENES  FCETIDUS. — Passet  found  this  organism 
(Fig.  3,  Passet)  in  the  pus  of  a  peri-rectal  abscess  This  bacillus 
grows  on  gelatin,  forming  a  delicate  white  or  grayish  layer  on  the 
surface,  but  causes  no  liquefaction.  When  cultivated  on  agar-agar 
and  potato  it  has  the  appearance  of  a  light  brown  glistening  layer, 
which  emits  a  very  offensive  odor.  In  milk  this  smell  is  not  pro- 
duced. This  organism  is  not  pathogenic  in  rabbits.  In  mice 
traces  of  the  culture  do  no  harm ;  the  injection  of  several  drops 
causes  septica3mia.  Injection  of  about  ten  minims  of  the  cultiva- 
tion into  guinea-pigs  causes  an  abscess  in  which  the  bacilli  alone 
are  found ;  direct  injection  into  the  circulation  causes  sepsis. 

FIG.  4. 


Bacillus  pyogenes  foetidus,  700  :  1.  Bacillus  pyocyaneus,  700 :  1. 

(PASSET.)  (FLUGGE.) 

10.  BACILLUS  PYOCYANEUS. — Ernst  found  in  blue  pus  two 
kinds  of  bacilli,  Fig.  4  (Fliigge),  which  he  designated  as  bacillus 
pyocyaneus.  Ledderhose  ("  Ueber  den  blauen  Eiter,"  Deutsche 
Zeitschrift  /.  Chirurgie,  B.  xviii.  Heft  3),  by  extensive  cultivations 
of  these  bacilli,  obtained  a  considerable  quantity  of  pyocyanin  and 
by  chemical  analysis  determined  its  formula  to  be  C14H14N2C.  In 
doses  of  one  gramme  as  muriate  of  pyocyanin  injected  into  the 
circulation  of  different  animals,  he  observed  no  toxic  symptoms. 
When  a  pure  culture  of  the  bacilli  was  injected,  he  observed  in- 
flammation and  suppuration,  and  attributes  this  result,  not  to  the 
presence  of  pyocyanin,  but  to  other  as  yet  unknown  phlogistic  and 
pyogenic  substances. 

Experimental  and  Clinical  Evidences  which  Prove  that  Pus-microbes 
are  the  Only  and  Essential  Cause  of  Suppuration. 

Rosenbach  found  that  in  dogs  and  rabbits  a  small  quantity  of  a 
pure  culture  of  the  staphylococcus  pyogenes  aureus  injected  under 
the  skin  produced  a  most  violent  suppurative  inflammation ;  cul- 


ESSENTIAL    CAUSE    OF    SUPPURATION.  8o 

tures  of  the  staphylococcus  pyogenes  albus  produced  the  same 
eftect.  Cultures  of  the  streptococcus  pyogenes  produced  only 
slight  inflammation  in  rabbits,  while  they  proved  very  fatal  in 
mice. 

Passet  ("Ueber  die  Aetiologie  und  Therapie  der  Impetigo,  des 
Furuukels  und  der  Sykosis,"  Monatshefte  f.  prakt.  Dermatologie, 
B.  vi.  No.  10,  1887)  took  a  pure  culture  of  the  staphylococcus 
pyogenes  aureus  the  size  of  a  pea  grown  upon  potato  and  mixed  it 
with  5  c.c.  of  distilled  water.  Of  this  fluid  he  injected  under 
the  skin  of  a  mouse  0.1  c.c.;  the  animal  recovered.  Another 
mouse  was  treated  in  the  same  manner,  but  0.4  c.c.  of  gelatin, 
liquefied  by  the  same  microbe,  was  used,  and  this  animal  died  in 
eighteen  hours.  Cocci  were  found  in  the  blood.  In  rabbits  and 
dogs,  a  subcutaneous  injection  of  1  c.c.  liquefied  gelatin-culture 
of  the  aureus  usually  produced  an  abscess  at  the  point  of  inocula- 
tion. If  the  dose  was  increased  to  5  c.c.  of  such  a  culture,  the 
animals  died  in  from  eighteen  to  twenty  hours,  at  the  same  time  a 
local  inflammation  was  found  at  the  point  of  injection.  In  all  of 
these  cases  the  blood  contained  numerous  cocci.  Of  the  culture  of 
the  streptococcus  it  was  found  necessary  to  inject  a  considerable 
quantity  in  order  to  produce  suppuration.  Liquefied  gelatin-cul- 
tures of  the  staphylococcus  pyogenes  aureus  and  albus,  in  doses 
of  1  c.c.,  injected  into  the  abdominal  cavities  of  rabbits,  were 
well  tolerated,  and  death  was  only  produced  when  the  dose  was 
increased  to  from  4  to  6  c.c.  Injection  of  cultures  of  the  strep- 
tococcus pyogenes  into  the  peritoneal  cavity  was  even  better  toler- 
ated, and  usually  had  to  be  repeated  several  times  to  produce  death 
from  peritonitis.  A  needle  dipped  into  a  culture  of  pus-microbes 
he  could  insert  into  joints  without  causing  suppuration  ;  but  the 
injection  of  from  0.3  to  0.5  c.c.  of  a  mixture  of  pus-microbes 
and  water  into  the  hip-joint  of  rabbits  produced  suppurative  arthri- 
tis, rupture  of  the  capsule,  and  diifuse  para-articular  phlegmonous 
inflammation  and  suppuration,  and  often  death  of  the  animal. 
Injection  of  one  or  two  drops  of  a  liquefied  gelatin-culture  of  the 
staphylococcus  aureus,  or  albus,  into  a  vein  of  a  rabbit  did  not 
produce  any  serious  disturbance,  but  if  the  dose  was  increased  to 
from  0.5  to  1,  it,  as  a  rule,  caused  a  fatal  disease.  In  such  cases, 
multiple  suppurating  foci  were  found  in  the  kidneys,  liver,  spleen, 
and  lungs,  with  pleuritic  and  peritoneal  effusions,  pericarditis  and 
myocarditis,  also  serous  and  purulent  effusions  into  joints  and  mus- 
cular abscesses.  A  pure  culture  on  potato  scraped  off  and  injected 
into  the  circulation  produced  mycotic  endocarditis.  Injection  of  a 
pure  culture  of  streptococcus  pyogenes  was  more  frequently  fol- 
lowed by  joint  complications  and  peritoneal  effusion.  The  effect 
of  the  introduction  of  pus-microbes  in  man  is  the  same  as  in 


86  SUPPUEATION. 

animals.  Garre  ("  Zur  Aetiologie  der  acut  eitrigen  Eutziiuduu- 
geu,"  Fortschritte  der  Medicin,  1885,  No.  6)  made  a  superficial 
abrasion  on  one  of  his  fingers  and  applied  a  pure  culture  of  the 
staphylococcns  pyogenes  aureus ;  the  only  symptom  observed  was 
a  slight  redness  eighteen  to  twenty-four  hours  after  the  inoculation. 
He  then  made  three  small  incisions  and  inoculated  himself  with  a 
larger  quantity  of  the  culture,  which  was  followed  by  a  slight  sub- 
epidermal  suppuration.  The  same  author  made  numerous  cultiva- 
tions from  pus  of  different  forms  of  acute  abscesses,  and  always 
succeeded  in  demonstrating  the  presence  of  one  or  more  of  the  pus- 
microbes.  From  the  product  of  acute,  diffuse  phlegmouous  inflam- 
mation the  culture  consisted  usually  of  streptococci. 

Fehleisen  repeated  the  same  experiments  with  cultures  of  the 
different  kinds  of  pus-microbes,  and,  if  he  succeeded  in  causing 
suppuration,  this  was  always  very  slight.  He  also  found  minute 
doses  administered  subcutaneously  harmless,  while  a  larger  quantity 
of  pus- microbes  suspended  in  water,  almost  without  exception, 
caused  abscesses,  and,  in  animals,  very  large  doses  produced  death 
from  sepsis  before  suppuration  could  take  place. 

Bockhardt  introduced  a  trace  of  the  mixed  cultivation  of  staphy- 
lococcus  aureus  and  albus  into  the  cutis  of  his  left  forefinger ;  after 
forty-eight  hours  a  small  abscess  had  formed,  and  was  opened,  and 
the  pus  contained  the  staphylococcus  pyogenes  aureus. 

He  also  made  on  himself  endermic  inoculations  with  a  mixture 
of  staphylococcus  pyogenes  aureus  and  albus.  Fourteen  hours  after 
injection  there  were  at  the  seat  of  inoculation,  in  a  space  about  the 
size  of  a  five-shilling  piece,  twenty-five  impetigo  pustules,  varying 
from  the  size  of  a  pin's  head  to  that  of  a  lentil,  a  few,  but  not  the 
majority,  of  these  being  traversed  by  hair.  They  contained  the 
cocci  employed.  Bumm  injected  pure  cultivations  of  staphylococcus 
pyogeues  aureus  into  the  subcutaneous  tissue  of  his  own  arm  and 
into  the  arms  of  two  other  persons.  In  each  instance  an  abscess 
developed,  which  varied  from  the  size  of  a  pigeon's  egg  to  that  of 
a  man's  fist,  according  to  the  time  which  elapsed  before  they  were 
opened,  and  these  abscesses  contained  the  same  species  of  microbes 
as  were  injected. 

Fehleisen  (u  Zur  Aetiologie  der  Eiteruug,  Arbeiteu  aus  der 
Chirurgischen  Klinik  der  Konigl.  Universitat,"  Berlin,  Dritter 
Theil.,  1887),  who  believes  that  the  ptomaines  produced  by  the  pus- 
microbes  are  the  direct  cause  of  suppuration,  has  also  made  numer- 
ous experiments  on  animals  by  injecting  pure  cultures,  or  pus.  In 
order  to  ascertain  whether  the  presence  of  atmospheric  air  had 
anything  to  do  with  the  formation  of  pus,  he  made  subcutaneous 
sections  of  muscles  and  tendons  with  a  tenotomy  knife  which  had 
been  dipped  in  a  mixture  of  water  and  pus-microbes,  and,  as  sup- 


ESSENTIAL    CAUSE    OF    SUPPURATION.  87 

puration  did  not  occur,  he  smeared  the  blade  of  the  tenotome  with 
a  pure  culture  of  pus- microbes  and  kept  the  instrument  under  a 
glass  globe  for  six  hours  for  the  liquid  to  dry  on  it,  and  repeated 
the  same  operation,  and  still  no  suppuration  followed.  In  two 
dogs  of  the  same  age,  he  dissected  up  a  triangular  flap  of  skin  over 
the  abdomen  with  the  base  toward  Poupart's  ligament,  and  in  one 
of  the  animals  infected  the  wound  with  a  pure  culture  of  pus- 
microbes  before  suturing,  while  in  the  other  the  wound  was  closed 
without  such  infection.  The  non-infected  wound  healed  by  primary 
intention,  while  in  the  other  animal  a  large  abscess  formed.  He 
also  exposed  the  femoral  vessels  in  animals,  and  inoculated  the  sur- 
face over  the  vessels  with  pus-microbes,  with  the  result  of  causing 
only  an  abscess,  but  never  progressive  septic  infection.  In  rabbits 
and  dogs,  the  injection  of  one  drop  of  pus  into  the  connective  tissue 
produced  no  reaction — absorption  taking  place.  In  both  of  these 
animals  the  injection  of  from  1  to  2  c.c.  of  pus  under  the  skin 
always  developed  large  abscesses.  In  a  rabbit,  0.4  c  c.  of  strep- 
tococci-containing pus  caused  death  in  forty  hours ;  suppuration  at 
the  point  of  injection.  Streptococcus  culture  was  obtained  from 
the  blood  taken  from  the  liver.  Wegner  ascertained  that,  in  order 
to  produce  suppurative  peritonitis  in  rabbits,  it  is  necessary  to  inject 
6  c.c.  of  pus,  and  in  dogs  25  c.c.  Fehleisen  injected  into  the 
peritoneal  cavity  of  rabbits  8  c.c.  of  streptococci-containing  pus, 
with  the  result  that  the  animals  were  almost  immediately  seized 
with  toxic  symptoms,  followed  by  death  in  twelve  hours.  After 
death,  double  pleuritis  and  peritonitis  were  found.  Streptococci 
could  be  cultivated  from  the  blood.  In  two  rabbits,  8  c.c.  of 
tubercular  pus  were  injected  into  the  peritoneal  cavity  without  pro- 
ducing any  immediate  symptoms  until  tuberculosis  developed.  In 
rabbits,  staphylococcus-containiug  pus  produced  no  constant  symp- 
toms. Some  died  after  an  injection  of  from  1  to  2  c.c.,  others 
recovered  after  injection  of  from  4  to  5  c.c.  From  these  experi- 
ments, he  came  to  the  conclusion  that  the  virulence  of  pus  does  not 
depend  upon  the  number  of  microbes  it  contains,  but  is  proportion- 
ate to  the  intensity  of  the  inflammation  in  the  individual  from 
which  it  was  taken. 

Zuckermann  (Aus  dem  Laboratorium  f.  Cliirurgie,  Pathologic  u. 
Therapie  der  k.  Universitat  zu  Kasan.\  as  the  result  of  his  own 
investigations  and  experiments,  formulates  his  own  ideas  in  refer- 
ence to  the  causes  of  suppuration  in  the  following  conclusions  : 

1.  Mechanical,  chemical,  or  thermal  influences,  if  microbes  are 
excluded,  do  not  produce  suppuration. 

2.  If  suppuration    followed  any  of  these   causes,    it  was    not 
without  the  admission  of  microbes. 

3.  Chemically-pure  substances  may  be  mycotically  impure ;  even 


88  SUPPURATION. 

some  disinfecting   agents   are,   it   appears,  not   always    free  from 
microbes. 

4.  As   causes  of  suppuration    the   following    microbes  can  be 
enumerated  :  staphylococcus  pyogenes   aureus,  albus,  and  citreus  ; 
streptococcus  pyogeues,  and,  in  foul    abscesses,  also    the   bacillus 
pyogenes  foetid  us. 

5.  Inoculations   with    staphylococcus   and    streptococcus    have, 
when  injected  in  large  quantities,  produced  local  suppuration,  or 
death  by  general  infection. 

6.  The  pus-microbes  must,  in  the  face  of  the  frequent  occurrence 
of  suppuration,  have  a  wide  diffusion  through  nature. 

7.  Pus-microbes  can  enter  the  organism  through  the  respiratory 
passages,  the   intestinal  canal,    and  skin.     Entrance  is   most  fre- 
quently effected  through  the  skin. 

8.  The   staphylococcus  and    streptococcus  are  found  most  fre- 
quently in  pus. 

The  same  writer  to  show  the  frequency  of  occurrence  of  the  dif- 
ferent kinds  of  pus-microbes,  has  tabulated  from  different  sources 
495  abscesses,  and  he  states  that  the  staphylococcus  was  present  in 
71  per  cent.,  the  streptococcus  in  16  per  cent.,  these  two  microbes 
together,  in  5.5  per  cent.,  and  the  remaining  pyogenic  microbes 
only  exceptionally. 

Tricomi  ("Referat,"  Berl  Mm.  Woehenschrift,  Jan.  23,  1888) 
made  a  bacteriological  examination  of  80  acute  abscesses,  8  phleg- 
monous  inflammations,  and  5  furuncles,  and  never  failed  in  finding 
the  microbes  of  suppuration.  He  makes  no  distinction  between 
the  streptococcus  and  staphylococcus  and  includes  both  forms 
under  the  term  micrococcus  pyogenes.  His  own  experiments  on 
mice,  rabbits,  and  guinea-pigs  have  led  him  to  the  opinion  that 
pus-microbes  have  a  specific  destructive  action  on  the  connective 
tissue,  and  he  asserts  that  their  pathogenic  action  is  limited  to  this 
tissue.  The  results  of  his  observations  on  animals  he  applies  to 
human  pathology,  and  attempts  to  establish  the  fact  that,  in  the 
formation  of  abscesses  in  the  internal  organs,  destructive  processes 
must  precede  and  prepare  the  soil  for  the  microbes. 

He  does  not  believe  that  indifferent  and  chemical  substances, 
mycotically  pure,  can  cause  suppuration. 

Watson  Cheyne,  in  his  admirable  lectures  on  suppuration,  puts 
himself  on  record  as  believing  that  no  aseptic  substances  or  chem- 
ical irritants  ever  cause  suppuration.  He  affirms  that  the  product 
of  inflammation  which  accumulates  at  the  point  of  implantation  or 
infection  in  such  cases  is  not  true  pus,  but  a  putty-like  substance 
which  is  more  consistent  than  pus  from  the  absence  of  ptomaines. 
He  asserts  that  for  the  formation  of  a  true  abscess  we  require  the 
peptonizing  ferment  produced  by  the  microorganisms,  or,  at  any 


THE    RELATION    OF    PTOMAINES    TO    SUPPURATION.      89 

rate,  of  a  chemical  substance  which  prevents  coagulation  of  the 
exuded  fluid.  He  describes  a  minute  abscess  as  containing  a  colony 
of  microbes  which,  when  fixed  in  the  tissues,  cause  a  limited  coagu- 
lation-necrosis of  the  tissues  in  immediate  contact  with  the  microbes 
by  the  action  of  the  ptomaines  ;  a  few  hours  later  a  zone  of  leuco- 
cytes aggregate  around  the  dead  tissues.  The  products  of  inflam- 
mation also  remain  fluid,  probably  also  from  the  peptonizing  effect 
of  the  microbes,  and  thus  an  abscess  is  formed. 

The  above  observations  are  conclusive  in  showing  that  pus- 
microbes  can  be  cultivated  from  the  pus  of  every  acute  abscess,  and 
that,  in  man  and  animals,  the  injection  of  a  sufficient  quantity  of  a 
pure  culture  into  the  tissues  is  followed  by  suppuration  ;  and  thus 
far,  positive  proof  has  been  furnished  of  the  direct  etiological  rela- 
tionship which  exists  between  pus-microbes  and  suppuration. 
Quite  recently  a  number  of  pathologists  have  gone  one  step  further, 
and  claimed  that  pus-microbes  are  not  the  direct  cause  of  suppura- 
tion, but  that  their  presence  is  essential  for  the  production  of  pto- 
maines, to  which  they  attribute  pyogenic  properties.  We  will, 
therefore,  consider 

The  Relation  of  Ptomaines  to  Suppuration. 

Grawitz  and  de  Bary  ("  Ueber  die  Ursachen  der  subcutanen 
Entziindung  und  Eiterung,"  Virchow's  Archiv,  B.  cviii.  S.  68), 
after  detailing  the  results  of  their  experiments  with  injections  of 
chemical  irritants  during  their  studies  on  pus-production,  give  an 
account  of  their  experiments  with  the  ptomaines,  of  pus-microbes. 
They  claim  that  these  ptomaines,  like  chemical  irritants,  prepare 
the  soil  in  the  tissues  for  the  growth  and  reproduction  of  pus- 
microbes  The  action  of  these  substances  becomes  apparent  by 
injection  of  sterilized  cultures  where  the  only  active  agents  could  be 
the  preformed  poisons.  They  injected  4  c.c.  of  a  sterilized  culture 
of  the  staphylococcus  pyogeues  aureus  under  the  skin  of  a  dog,  and 
produced  suppuration.  The  contents  of  the  abscess  were  examined 
for  microbes,  but  none  were  found.  They  claim  that  the  presence  of 
oxygen  is  of  the  greatest  importance  in  the  production  of  pto- 
maines. 

Grawitz  ("  Ueber  die  Bedeutung  des  Cadaverins  f.  das  Entste- 
hen  von  Eiterung,"  Virchow's  Archiv,  B.  ex.  Heft  1)  experi- 
mented with  a  pure  preparation  of  cadaveriu,  prepared  by  Brieger 
from  bacteria.  This  belongs  to  the  class  of  non-toxic  cadaver 
alkaloids,  and  is  a  colorless  fluid,  the  chemical  formula  of  which  is 
identical  with  pentamethylendiomin  ;  a  2J  per  cent,  solution  of 
this  substance  destroyed  the  staphylococcus  pyogenes  aureus  in  an 
hour,  and  a  small  quantity  added  to  a  culture  of  pus-microbes 


90  SUPPURATION. 

arrested  further  growth.  A  solution  absolutely  free  from  microbes, 
injected  under  the  skin  of  animals,  according  to  strength  and  quan- 
tity used,  produced  cauterization  or  inflammation,  terminating  in 
suppuration  or  inflammatory  oedema,  followed  by  resolution  and 
absorption.  The  pus  produced  by  cadaveriu  contained  no  bacteria 
as  long  as  the  skin  remained  intact.  The  injection  of  a  mixture  of  a 
solution  of  cadaverin  and  pus-microbes  caused  a  progressive  phleg- 
monous  inflammation. 

Scheuerlen  ("  Weitere  Untersuchungen  liber  die  Entstehuug 
der  Eiterung,  ihr  Verhaltniss  zu  den  Ptomaiuen  und  zur  Blutgeriu- 
nung,"  Mittheilungen  cms  der  Chirwgischen  Klinik  der  Koniglichen 
Universitdt.  Berlin,  Dritter  Theil.  1887)  has  on  a  previous  occasion 
shown  that  croton  oil,  turpentine,  and  other  irritants  cannot  produce 
suppuration.  In  all  cases  in  which  pus  was  produced  by  any  of 
these  agents  it  contained  bacteria.  He,  therefore,  takes  it  for 
granted  that  pus  can  only  be  produced  by  microorganisms.  How 
this  is  done  is  difficult  to  prove.  The  action  of  pus-microbes  upon 
the  tissues  must  be  either  physical  or  chemical.  The  action  of 
ptomaines  on  the  living  tissues  was  studied  by  Pauum  as  early  as 
1856,  and  later  by  Bergmann  and  his  scholars.  Recently  this  sub- 
ject has  been  studied  in  a  systematic  manner  by  Brieger.  Scheuer- 
len was  the  first  to  study  their  local  effects.  He  introduced  into 
the  subcutaneous  connective  tissue  of  rabbits  aseptic  glass  capsules 
containing  sterilized  putrid  infusion  of  meat ;  the  wounds  were 
treated  under  the  strictest  antiseptic  precautions,  and  healed  by 
primary  union.  After  the  wound  was  healed,  he  broke  off  subcu- 
taneously  both  ends  of  the  glass  capsule,  so  as  to  bring  the  fluid  it 
contained  into  contact  with  the  tissues.  Three  to  six  weeks  after 
implantation  of  the  capsule  the  parts  were  incised  and  examined. 
The  ends  of  the  capsule  were  always  found  to  contain  a  few  drops 
of  thin  yellow  pus,  which,  under  the  microscope,  showed  all  the 
characteristic  appearances  of  this  fluid.  The  surrounding  tissues 
were  not  affected.  Cultivation  experiments  yielded  negative  results. 
When  the  capsules  were  broken,  the  ptomaines  came  in  contact 
with  the  leucocytes  which  had  accumulated  around  the  foreign 
body,  and  by  their  local  toxic  effects  transformed  them  into  pus 
corpuscles,  while  no  evidences  of  local  infection  were  present,  which 
shows  conclusively  that  the  transformation  of  the  leucocytes  into 
pus  corpuscles  was  accomplished  by  the  ptomaines.  In  about 
twenty  experiments  the  pus  was  found  only  inside  the  capsule.  In 
the  cases  in  which  the  tube  had  been  implanted  for  eight  weeks, 
the  conditions  remained  the  same.  Weigert  has  repeatedly  shown 
that  the  difference  between  a  purulent  and  fibrinous  exudation  can 
be  readily  demonstrated,  as  the  former  does  not  coagulate,  although 


RELATION    OF    PTOMAINES    TO    SUPPURATION.         91 

white  corpuscles  and  plasma  may  be  present.  Klemperer  believes 
that  this  is  due  to  a  previous  destruction  of  fibrinogen  by  the 
microorganisms.  The  putrid  meat  infusion  used  by  Schenerleii 
caused  limited  suppuration,  and  on  that  account  it  must  also  have 
possessed  the  property  to  prevent  coagulation.  To  prove  this,  he 
made  the  following  experiment:  The  abdomen  of  a  rabbit  was 
opened  while  the  animal  was  under  the  influence  of  chloroform, 
and  blood  was  drawn  directly  from  the  aorta  into  a  glass  tube  con- 
taining putrid  extract  of  meat.  As  the  fluids  gradually  became 
mixed,  the  blood  assumed  a  brownish-red  color ;  coagulation  did 
not  take  place  alter  hours  and  days,  while  in  the  control  experi- 
ments, with  solution  of  salt,  the  blood  coagulated  firmly  after  the 
lapse  of  a  few  minutes.  Microscopical  examination  of  the  mixture 
of  blood  and  putrid  fluid  showed  no  fibrin  and  no  rouleaux  of  red 
blood- corpuscles.  Both  the  red  and  white  corpuscles  were  con- 
tracted and  corrugated.  He  next  made  thirty  cultures  of  the  staphy- 
lococcus  pyogenes  aureus  on  agar-agar  gelatin,  and  the  same 
number  of  cultures  of  the  albus,  and  after  completion  of  their 
growth,  fourteen  days  later,  he  sterilized  them  with  boiling  water, 
and  after  shaking  the  fluid  removed  the  cultures  and  boiled  them 
for  a  few  minutes,  and  finally  filtered  them  ;  and  thus  obtained 
about  150  c.c.  of  a  light  yellow  fluid.  This  was  reduced  to  8 
c.c.  by  boiling ;  when  used,  the  fluid  was  again  filtered.  The  fil- 
trate was  put  in  capsules  and  introduced  into  the  subcutaneous 
tissues  of  animals  in  the  same  manner  as  in  the  preceding  experi- 
ments. The  suppuration  which  followed  was  again  found  to  be 
limited  to  the  inside  of  the  broken  glass  capsules,  the  same  as  in 
the  experiments  with  the  sterilized  putrid  meat  infusion.  The 
cadaverin  and  putrescin,  two  ptomaines  prepared  by  Brieger,  were 
next  experimented  with  in  the  same  manner.  In  preventing 
coagulation  the  results  were  even  more  marked  than  with  the  former 
substances.  Both  also  produced  the  same  localized  suppuration  in 
the  interior  of  the  broken  glass  capsule.  Cadaveriu  has  lately 
been  produced  chemically  by  Ladeuberg  from  trimethyleu-cyanuret 
as  pentamethylendiomin. 

These  experiments  leave  no  doubt  that  ptomaines  exert  a  chemi- 
cal influence  on  leucocytes  and  embryonal  tissue,  which  transforms 
these  tissues  into  pus  corpuscles.  The  suppuration  which  is  thus 
produced,  however,  never  extends  beyond  the  tissues  which  are 
brought  in  direct  contact  with  them,  and,  therefore,  always  remains 
circumscribed.  In  this  respect  the  experiments  just  cited  do  not 
correspond  with  suppuration  as  we  meet  it  at  the  bedside,  as  here 
from  the  same  causes,  and  apparently  under  the  same  conditions, 
the  process  presents  the  greatest  variations  in  reference  to  its  inten- 
sity and  extent.  In  one  case  the  suppuration  remains  circum- 


92  SUPPURATION. 

scribed,  resulting  in  a  furuncle;  in  others  the  regional  infection 
is  more  extensive,  and  a  diffuse  phlegrnonous  inflammation  is  the 
result;  while  in  a  third  class,  the  local  infection  leads  to  general 
invasion,  and  the  patient  dies  of  sepsis  or  pyaemia.  The  clinical 
forms  are  noted  for  the  progressive  character  of  the  infection, 
which  is  due  to  the  multiplication  of  microorganisms  within  the 
body,  and  the  production  of  ptoman'ies  proportionate  in  amount  to 
the  number  of  microbes  present.  Practically,  the  matter  remains 
the  same  as  before  it  was  known  that  ptomaines  could  cause  sup- 
puration, as  pus-microbes  must  be  introduced  into  the  organism 
before  ptomaines  can  be  produced,  and  for  the  practical  surgeon  it 
is  immaterial  to  know  whether  suppuration  is  the  direct  or  indirect 
result  of  the  presence  of  pus-microbes.  Scientifically,  however, 
this  question  has  an  important  bearing,  and  has  again  awakened 
interest  in  the  question  : 

Can  Suppuration  be  Produced  by  Chemical  Irritants  ? 

Grawitz  and  de  Bary  produced  by  subcutaneous  injections  of 
turpentine,  variable  results  in  different  animals.  Injections  of  tur- 
pentine, with  or  without  pus-microbes,  produced  inflammation,  but 
no  suppuration  in  rabbits  and  guinea-pigs ;  while  in  dogs  the  same 
injections  invariably  caused  suppuration.  Crotou  oil  was  found 
to  possess  no  influence  in  retarding  the  growth  of  pus-microbes. 
Injection  experiments  demonstrated  that  this  substance  in  small 
quantities  in  the  connective  tissue  of  rabbits  caused  a  serous  or 
fibrinous  exudation,  while  larger  doses  acted  as  a  caustic,  and  were 
only  occasionally  followed  by  suppuration.  Injections  of  a  mix- 
ture of  pus-microbes  and  croton  oil  always  caused  suppuration. 
They  maintained  that  certain  chemical  substances,  used  in  a  definite 
degree  of  concentration,  injected  into  the  subcutaneous  tissue  of 
animals,  prepared  the  tissues  for  the  growth  of  pus-microbes. 

In  a  later  series  of  experiments  on  the  production  of  suppuration 
Grawitz  ("  Beitrag  zur  Theorie  der  Eiterung,"  Virchow's  Archiv, 
B.  cxvi.  S.  116)  obtained  similar  results,  and  still  maintains  that 
aseptic  turpentine,  when  introduced  in  sufficient  quantity  into  the 
tissues,  causes  suppuration.  Inoculations  of  different  nutrient  media 
with  such  pus  showed  that  it  was  sterile.  He  maintains  that  tur- 
pentine does  not  destroy  pus-microbes.  He  also  found  that  pus 
produced  by  turpentine  injections  had  a  distinctive  effect  on  pus- 
microbes.  This  action  of  sterile  pus  he  attributes  not  to  the  presence 
of  ptomaines  but  to  the  action  of  its  albuminous  constituents.  His 
experiments  led  also  to  the  important  observation  that  when  gelatin 
cultures  are  over-saturated  with  albumin  or  peptone,  pus-microbes 
will  no  longer  grow  upon  them. 


CAN    SUPPURATIOX    BE    PRODUCED    BY  CHEMICALS  ?      93 

Councilman  ("Zur  Aetiologie  der  Eiterung,"  Virchow's  Arehiv, 
B.  xcii.  S.  217—230)  introduced  turpentine  and  croton  oil  in  aseptic 
glass  capsules  into  the  connective  tissue  of  animals,  and  after  the 
wound  had  healed  and  the  capsules  had  become  encysted,  ruptured 
them  subcutaneously.  He  observed  that  these  substances  caused  a 
circumscribed  suppuration. 

Uskoif  ("  Giebt  es  eine  Eiterung,  unabhangig  von  niederen 
Organisrnen?"  Virchow's  Archiv,  B.  Ixxxv.,  1881)  found  by  his 
experiments  that  a  considerable  quantity  of  indifferent  substances, 
such  as  milk,  olive  oil,  etc.,  if  injected  subcutaneously  in  animals, 
either  at  once,  or  by  repeating  the  injection  from  time  to  time, 
caused  suppuration,  and  that  turpentine  administered  in  this  manner 
always  acted  as  a  pyogenic  agent. 

Orthmann  ("  Ueber  die  Ursachen  der  Eiterbildung,''  Virchow's 
Arehiv,  B.  xc.  S.  544-554),  under  Rosenbach's  supervision,  re- 
peated Uskoff's  experiments,  and  by  resorting  to  most  strict  anti- 
septic precautions  could  not  verify  the  correctness  of  his  conclusions 
in  regard  to  the  pyogenic  properties  of  indifferent  substances.  His 
experiments  with  croton  oil,  turpentine,  and  metallic  mercury  re- 
sulted in  inflammation  and  suppuration.  Cultivation  experiments 
with  pus  thus  produced  showed  that  it  was  sterile. 

Scheuerlen  ("  Die  Entstehung  und  Erzeugung  der  Eiteruug  durch 
chemische  Reizmittel,"  1887)  made  a  series  of  very  carefully  con- 
ducted experiments,  and  came  to  the  conclusion  that  aseptic  sub- 
stances never  produced  suppuration.  He  modified  Councilman's 
method  by  substituting  capillary  glass  tubes  for  the  glass  capsules, 
which  were  rendered  perfectly  aseptic,  and  were  then  charged  with 
from  one  to  four  drops  of  turpentine,  after  which  they  were  sealed 
in  the  flame  of  a  spirit  lamp.  They  were  inserted  into  the  tissues 
through  a  long,  hollow  needle,  in  order  to  avoid  the  necessity  of 
making  an  incision.  After  the  glass  was  put  in  the  proper  place 
the  needle  was  withdrawn,  and  the  puncture  closed  with  iodotbrm 
collodion.  After  the  puncture  was  healed  the  glass  tube  was  broken 
underneath  the  skin.  He  extended  his  investigations  to  other  irri- 
tating substances  aside  from  turpentine,  but  in  no  instance  was  the 
experiment  followed  by  suppuration. 

Quite  recently,  Grawitz  and  de  Bary  ("  Ueber  die  Ursachen  der 
subcutanen  Entziinduug  und  Eiteruug,"  Virchow's  Archiv,  B.  cviii. 
S.  67-103)  again  upheld  the  theory  that  suppuration  can  be  pro- 
duced by  irritating  substances  independently  of  microorganisms. 
Among  the  many  important  conclusions  drawn  from  their  numer- 
ous experiments  may  be  mentioned  the  following : 

1.  Weak  solutions  of  nitrate  of  silver,  0.5  per  cent.,  if  adminis- 
tered subcutaueously,  are  absorbed ;  strong  solutions,  5  per  cent. 


94  SUPPURATION. 

in  dogs  produce   suppuration,  in    guinea-pigs  only  inflammatory 
swelling. 

2.  To  a  number  of  chemical  agents,  such  as  concentrated  solution 
of  salt,  acids,  etc.,  a  considerable  quantity  of  a  culture  of  staphylo- 
coccus  can  be  added  without  suppuration  following  the  injection. 

3.  In  rabbits  and  guinea-pigs,  even  a  large  quantity  of  turpentine 
can  be  injected  without  causing  suppuration.     In  dogs,  turpentine 
injection  into  the  subcutaneous  tissue  acts  as  a  pyogenic  substance 
par  excellence.     These  experimenters  affirm  that  the  microbes  of 
suppuration  alone  cannot  produce  pus  in  the  subcutaneous  tissue  in 
dogs  and  rabbits.     On  the  other  hand,  they  claim  that  chemical 
substances,  mycotically  pure,  can,  under  certain  conditions,  produce 
suppuration,  and  must,  when  used  in  proper  doses  and  concentra- 
tion in  the  right  kind  of  animals,  produce  suppuration  without  fail. 

Nathan  (Archivf.  klin.  Chir.,  Bd.  xxxvii.  8.  875)  makes  an  inter- 
esting contribution  on  the  etiology  of  suppuration  in  view  of  the 
fact  that  Grawitz  and  de  Bary  assert  that  ammonia,  silver  nitrate, 
and  turpentine  injected  subcutaueously  into  the  tissues  of  dogs  pro- 
duce a  suppuration  in  which  no  microbes  can  be  found.  He  used 
dogs  in  his  experiments;  the  point  of  injection  was  shaved  and 
carefully  disinfected  with  sublimate  1  :  1000 ;  the  substance  used 
was,  after  careful  sterilization,  injected  by  means  of  a  needle  thor- 
oughly purified  by  heat.  During  the  whole  experiment  the  field 
of  operation  was  irrigated  with  sublimate  solution.  It  was  found 
that  abscesses  did  at  times,  but  not  invariably,  appear  as  a  result  of 
these  injections.  Plate  cultures  always  showed  that  these  abscesses 
contained  microorganisms,  though  both  cover-glass  preparations  and 
test-tube  cultures  failed  to  demonstrate  them.  The  development  of 
microorganisms  was  explained  by  the  theory  that  by  constant  lick- 
ing the  dogs  infected  the  puncture. 

Janowski  ("  Ueber  die  Ursachen  der  acuten  Eiterung,"  Ziegler's 
Beitrage  zur  path.  Anatomie,  Bd.  vi.  Heft  3)  experimented  with  ster- 
ilized oil  of  turpentine  on  dogs  and  rabbits,  producing  by  subcu- 
taneous injections  suppuration  in  the  former  animal  in  a  few  days, 
while  in  the  rabbits  the  suppurative  process  was  delayed  four  to  six 
weeks.  With  caustic  ammonia  he  obtained  only  negative  results, 
which  led  him  to  assert  that  when  this  substance  caused  suppuration 
in  the  hands  of  other  experimenters,  it  must  have  been  contami- 
nated with  pus-producing  microbes. 

P.  Kaufman u  ("  Ueber  den  Einfluss  des  Digitoxins  auf  die 
Enstehung  Eitriger  Phlegmone,"  Arcliiv  f.  Exp.  Pathologic,  Bd. 
xxv.  S.  397)  has  shown  experimentally  that  digitoxiu  when  injected 
subcutaneously  into  the  tissues  of  animals  produces  suppuration 
independently  of  pus-microbes.  In  dogs  this  result  followed  iujec- 


CAN    SUPPURATION    BE    PRODUCED    BY    CHEMICALS?      95 

tions  in  doses  of  from  one-half  to  one-third  of  a  milligramme 
dissolved  in  alcohol. 

From  a  clinical  aspect,  the  absence  of  pus-microbes  in  non-puru- 
lent inflammatory  products  speaks  strongly  in  favor  of  a  microbic 
cause  of  suppuration. 

Ruiys  ("  Ueber  die  Ursacheu  der  Eiterung,"  Deutsche  med. 
Wochenschrift,  1885,  No.  48)  made  some  exceedingly  interesting 
experiments  on  the  pyogenic  action  of  different  substances,  selecting 
the  anterior  chamber  of  the  eye  as  the  seat  for  injection.  The 
results  of  his  experiments  were  such  that  he  claimed,  in  a  most 
positive  and  emphatic  manner,  that  suppuration  never  takes  place 
without  micoorgauisms. 

Biondi  expressed  himself  to  the  same  effect. 

If  we  think  for  a  moment  how  difficult  it  is  in  experimenting 
on  animals  with  indifferent  substances  and  chemical  irritants  to 
procure  for  the  seat  of  injection  a  perfectly  aseptic  condition,  it  is 
not  difficult  to  conceive  that  opinions  still  differ  in  regard  to  the 
immediate  cause  of  suppuration.  At  the  same  time,  Watson 
Cheyne  has  shown  most  conclusively  in  his  article  on  "  Suppu- 
ration and  Septic  Diseases/'  to  which  frequent  allusion  has  been 
made,  that  the  number  of  bacteria  introduced  greatly  modifies  not 
only  the  intensity  of  symptoms,  but  also  the  character  of  the  disease. 
His  experiments  were  made  with  cultivations  of  Mauser's  proteus 
vulgaris.  He  estimated  that  -^th  c.  c.  of  an  undiluted  cultiva- 
tion of  this  microbe  contains  225,000,000  of  bacteria,  and  when 
this  quantity  was  injected  into  the  muscular  tissue  of  a  rabbit  it 
produced  speedy  death,  ^th  c.  c.  administered  in  the  same 
manner  caused  an  extensive  abscess  at  the  point  of  injection,  and 
death  of  the  animal  in  six  or  eight  wreeks.  Doses  of  less  than  -g-^yo-th 
c.  c.  produced  no  effect — in  fact,  doses  of  less  than  ^-th  to  y^o"th 
c.  c.,  or,  in .  other  words,  fewer  than  about  18,000,000  bacteria, 
seldom  caused  any  result.  The  same  observer  found  that  in  the 
case,  of  staphylococcus  pyogenes  aureus  that  it  was  necessary  to 
inject  something  like  1,000,000,000  cocci  into  the  muscles  of  rab- 
bits, in  order  to  cause  a  rapidly  fatal  result,  while  250,000,000 
produced  a  small  abscess.  In  the  case  of  the  tetanus  bacillus,  death 
did  not  occur  in  rabbits  when  fewer  than  1000  bacilli  were  intro- 
duced. He  believes  that  the  preformed  ptomaines  in  these  cases 
alter  the  result.  It  is  therefore  quite  possible  that,  in  the  experi- 
ments in  which  injection  of  pus-microbes  did  not  produce  suppura- 
tion, an  insufficient  number  of  cocci  were  injected  to  produce  the 
desired  result,  and  that  where  inert  substances  and  chemical  irritants 
caused  suppuration  the  injected  material  was  contaminated,  or  that 
infection  at  the  point  of  injection  occurred  through  the  wound  or 
subsequently  through  the  circulation.  The  latter  mode  of  infection 


96  SUPPUKATION. 

should  always  be  borne  in  mind  where  the  presence  of  an  aseptic 
body  in  the  living  tissues  has  apparently  been  the  cause  of  suppu- 
ration. The  tissues  altered  by  the  action  of  chemical  irritants 
constitute  a  foreign  substance  which  may  determine  localization  of 
floating  microbes,  while,  at  the  same  time,  the  chemical  alterations 
which  they  have  caused  in  the  tissues  have  prepared  a  favorable 
soil  for  their  reproduction.  Practically,  in  man,  suppuration  with- 
out microorganisms  is  only  possible  on  the  surface  of  the  body, 
as  the  products  of  a  suppurative  inflammation  in  any  of  the 
internal  organs  always  show  the  presence  of  pyogenic  microbes 
which  can  be  cultivated,  and  it  is  only  rational  to  conclude  that 
the  inflammation  and  subsequent  suppuration  were  caused  by  pyo- 
genic microorganisms  or  their  products,  the  ptomaines. 

Pus-microbes  in  Different  Suppurative  Affections. 

Direct  infection  with  pus-microbes  can  only  take  place  through  the 
cutaneous  and  other  accessible  surfaces  or  through  wounds.  Suppu- 
ration in  the  interior  of  the  body,  in  the  absence  of  a  wound  or 
other  recognizable  infection-atrium,  must  be  considered  in  the  light 
of  an  auto-infection  with  pyogenic  microbes. 

1.  SUPPUKATIVE  AFFECTIONS  OF  THE  SKIN. — Longard  ("Ueber 
Folliculitis  abscedeus  infantum,"  Archivf.  Kinderheilkunde,  Bd.  viii. 
Heft  5,  ]  887")  has  made  a  careful  microscopi co-bacteriological  exam- 
ination of  nine  cases  of  furunculosis  in  young  children.  In  four  of 
these  cases  he  found  the  staphylococcus  pyogeues  albus  alone,  in 
five  cases  in  combination  with  the  staphylococcus  pyogeues  aureus; 
the  identity  of  these  microbes  with  those  described  by  Rosenbach 
was  demonstrated  by  cultivations  and  experiments  on  rabbits.  The 
microbes  were  not  found  in  the  fecal  discharges  of  the  patients,  but 
were  found,  in  small  numbers,  in  the  diapers  of  healthy  unclean 
children,  as  well  as  in  the  diapers  of  those  stiffening  from  follicu- 
litis.  He  believes  that  the  pus-microbes  were  the  direct  cause  of 
the  affection,  and  that  the  infection  took  place  through  the  sweat- 
glands,  as  the  microbes  were  found  in  abundance  upon  the  inner 
surface  of  the  membrana  propria  of  these  appendages  of  the  skin. 
As  soon  as  they  reached  the  subcutaneous  connective  tissue  they 
produced  suppurative  inflammation. 

Experiments  on  dogs  and  rabbits,  by  cutaneous  inoculations  with 
pus-microbes  cultivated  from  the  furuncles,  produced  a  slight  swell- 
ing and  redness,  and  in  some  instances  the  formation  of  small  pus- 
tules. The  result  was  always  the  same  whether  the  pus  was  taken 
from  the  cultivation  grown  from  a  furuncle,  a  suppurating  wound 
that  healed  without  fever,  or  from  a  pysemic  patient.  The  cuta- 
neous inoculation  experiments  of  Garre,  Bockhart,  and  Bumm  upon 


PUS-MICROBES    IN    SUPPURATIVE    AFFECTIONS.       97 

themselves  have  been  previously  referred  to,  and  they  prove  that 
many  of  the  circumscribed  suppurative  affections  of  the  skin  are 
caused  by  direct  inoculation  with  pus-microbes  which  enter  the 
connective  tissue,  either  through  a  slight  abrasion  or  through  the 
glands  of  the  skin. 

2.  SEROUS  CAVITIES. — A  most  interesting  investigation  of  the 
conditions  under  which  infection  of  the  peritoneum  can  take  place 
has  been  made  by  Grawitz  ("  Statistischer  und  experimentell 
pathologischer  Beitrag,"  Charite"  Annalen,  Bd.  xi.  S.  770).  From 
his  own  experiments  he  came  to  the  conclusion  that  the  injection 
into  the  healthy  peritoneal  cavity  of  schizomycetes,  pyogenic  as 
well  as  non-pyogenic,  produced  no  unfavorable  results.  Perito- 
nitis was  caused  only  when  the  microbes  were  mixed  with  a  caustic 
fluid,  or  when  the  peritoneal  cavity  contained  a  fluid  which  could 
serve  the  purpose  of  a  nutrient  medium  ;  also,  when  the  amount  of 
fluid  injected  exceeded  the  absorbing  capacity  of  the  peritoneum  ; 
or,  finally,  if  the  peritoneum  was  injured  at  the  same  time,  or  the 
abdomen  was  opened  by  a  penetrating  wound.  Strange  as  it  may 
appear,  he  claims  that  the  injection  into  the  peritoneal  cavity  of 
intestinal  contents  caused  no  peritonitis  as  long  as  the  punctured 
wound  remained  aseptic. 

Leyden  ("Ueber  spontane  peritonitis,"  Deutsche  med.  Wochen- 
schrift,  1884.  p.  212)  demonstrated  the  presence  of  streptococci  in 
the  exudations  of  cases  apparently  spontaneous  peritonitis. 

Garre  ("  Bacteriologische  Untersuchungen  von  serosen  Trans  und 
Exsudaten  uud  Atheromen,"  Corresbl.  /.  Sehwdzerdrzte,  1886,  No. 
17)  examined  carefully  for  the  presence  of  microorganisms  in  hydro- 
cele  fluid,  serous,  peritoneal,  and  pleural  effusions,  and  the  contents 
of  joints  the  seat  of  serous  synovitis,  etc.,  by  means  of  microscopi- 
cal examination  and  cultivation  experiments,  always  with  negative 
results. 

The  same  author  ("  Bacteriologische  Untersuchuugeu  des  Bruch- 
wassers  eingeklemmter  Hernieu,"  Fortschritte  der  Mediein,  B.  x. 
S.  486-490),  in  order  to  test  the  observations  of  Nepveau,  accord- 
ing to  whom  the  transuded  fluid  in  a  heroial  sac  constantly  con- 
tains bacteria,  examined  eight  cases  of  incarcerated  hernia. 
Although  the  microscope  was  used  together  with  delicate  reagents 
for  microorganisms  and  cultivations  in  gelatin,  bacteria  were  found 
in  only  a  few  instances.  The  fluid  in  the  sac  of  non-incarcerated 
herniaB  examined  by  these  methods  was  found  absolutely  sterile. 
Analysis  of  all  the  cases  examined  demonstrated  that  the  length  of 
time  the  incarceration  has  existed  has  no  significance  as  regards  the 
presence  of  bacteria;  since,  in  recent  cases,  positive  results  were 
obtained,  while  in  a  case  in  which  incarceration  had  existed  for 
eight  days  the  result  was  negative.  Furthermore,  the  odor  of  the 

7 


98  SUPPURATION. 

fluid  is  no  indication  of  the  presence  of  bacteria,  as  these  may  be 
absent  even  in  fluid  having  a  fecal  odor.  In  cases  in  which  the 
bowel  becomes  gangrenous,  bacteria  pass  through  its  walls  and 
death  is  caused  by  septic  peritonitis. 

Frankel  ("  Ueber  puerperale  Peritonitis,"  Deutsche  med.  Wochen- 
sckrift,  1884,  p.  212)  has  found  the  streptococcus  pyogenes  in  a 
great  variety  of  puerperal  diseases ;  especially  in  cases  in  which 
the  local  affection  implicated  the  lymphatic  vessels.  In  such  cases, 
the  microbes  found  entrance  into  the  pelvic  tissues  from  abrasions 
or  ulcers  in  the  vagina,  and  by  extension  of  the  inflammatory  pro- 
cess the  broad  ligaments  and  the  peritoneum  are  successively 
reached  ;  after  the  peritoneum  has  once  been  reached,  rapid  diffu- 
sion takes  place,  and  finally  the  diaphragm  and  pleura  are  impli- 
cated in  the  same  process,  and  the  microbes  reach  the  blood  and 
cause  sepsis  and  pyaBmia. 

Weischelbaurn  ( Centralblatt  f.  Chirurgie,  August  17,  1889)  has 
shown  that  peritonitis  is  not  always  caused  by  pus-microbes  as  has 
been  heretofore  believed ;  he  has  found  the  diplococcus  of  pneu- 
monia unaccompanied  by  any  other  microorganism  in  three  cases 
of  peritonitis.  In  one  case  peritonitis  and  acute  pneumonia  existed 
at  the  same  time ;  in  the  other,  double  pleuritis  followed  the  peri- 
tonitis; but  in  the  last  case  the  peritonitis  was  undoubtedly  pri- 
mary and  in  the  absence  of  any  other  microbes  in  the  products  of 
the  inflammation  must  have  been  caused  by  the  diplococcus  of 
Friedlander. 

Orth  (British  Medical  Journal,  March  1,  1890)  has  shown  that 
the  pathogenic  properties  of  pus-microbes  are  strongly  modified  by 
certain  preexisting  pathological  conditions,  although  large  doses  of 
pure  cultures  of  the  staphylococcus  and  streptococcus  injected  into 
the  peritoneal  cavity  of  rats  failed  to  cause  any  lesion  of  the  perito- 
neum, the  same  microbes  in  the  same  doses  caused  fatal  results 
when  mixed  with  material  which  could  only  be  absorbed  slowly. 
Preexisting  disease  of  the  peritoneum  favored  the  action  of  the 
microbes  ,  in  ascitic  animals  a  very  small  quantity  of  a  culture  of 
staphylococcus  caused  septic  peritonitis.  The  same  result  followed 
when  any  intra-abdominal  structure  was  wounded.  These  experi- 
ments show  the  great  danger  which  may  follow  infection  of  the 
peritoneum  after  laparotomy,  especially  if  fluids  or  solid  particles 
are  allowed  to  remain  after  the  operation. 

Fraukel  (Berl  klin.  Wochenschrift,  May  14,  1888)  made  a  bac- 
teriological study  of  twelve  cases  of  empyema.  In  three  cases  in 
which  no  special  cause  could  be  traced  the  pus  contained  exclusively 
the  streptococcus  pyogenes.  In  three  cases  the  pus  contained 
only  pueumococci.  Other  authors  have  found,  in  such  cases,  also 
other  pus-microbes.  Frankel  thinks  that  when  this  is  the  case, 


PUS-MICKOBES    IN    SUPPUKATIVE    AFFECTIONS.       99 

they  have  been  deposited  ID  consequence  of  a  secondary  invasion. 
The  presence  of  streptococci  in  the  pus  from  a  suppurating  pleural 
cavity  presents  nothing  characteristic,  as  the  microbe  is  also  found 
in  cases  in  which  the  empyema  is  secondary  to  pneumonia  and 
tuberculosis.  On  the  other  hand,  he  assigns  to  the  pneumococcus 
in  pus  removed  from  a  pleural  cavity  a  diagnostic  significance,  as  it 
proves,  beyond  all  doubt,  that  the  suppurative  pleuritis  occurred  in 
the  course  of  a  pneumonia  as  a  secondary  affection,  consequently  its 
presence  in  the  pus  is  positive  proof  that  a  pneumonia  exists,  or  has 
existed,  even  if  the  clinical  and  physical  symptoms  were  not  suffi- 
ciently clear  to  indicate  its  existence.  In  four  cases  the  empyema 
had  a  tubercular  origin,  in  two  of  which  pneumothorax  existed  at 
the  same  time.  The  presence  of  the  bacillus  of  tuberculosis  in  the 
pus  is  not  easy  to  demonstrate,  but  the  absence  of  this  microbe  is  no 
sign  that  the  disease  is  not  tubercular,  as  inoculations  with  such 
pus  in  animals  almost  constantly  produce  typical  tuberculosis.  In 
the  pus  of  tubercular  pyo-pnenmothorax,  if  microorganisms  are 
present,  the  bacillus  of  tuberculosis  can  be  found,  and  the  pus  shows 
no  tendency  to  undergo  putrefactive  changes,  in  contradistinction 
to  empyema  occurring  in  non-tubercular  subjects,  in  whom  spon- 
taneous discharge  through  the  bronchial  tubes  takes  place. 

In  the  discussion  on  FrankePs  paper,  Senator  maintained  that 
putrefaction  is  prevented  by  the  parenchyma  of  the  lungs  acting  as 
a  filter,  preventing  ingress  of  bacteria  with  the  inspired  air,  and  by 
the  presence  of  a  large  amount  of  carbonic  acid  gas  in  the  air  of  the 
cavity,  as  it  is  well  known  that  microbes  do  not  thrive  as  well  in 
such  an  atmosphere  as  in  ordinary  air.  Fraukel  believes  that  the 
absence  of  putrefaction  in  such  cavities  is  due  to  the  fact  that  few, 
if  any  organisms,  except  tubercle  bacilli,  are  present  in  pus,  a'nd 
these  do  not  cause  putrefaction.  It  seems  that  tubercular  pus  does 
not  furnish  a  favorable  soil  for  the  growth  of  other  germs. 

Ehrlich  (Berl  Uin.  Woclienschrifi,  May  14,  1888)  has  made  a 
bacteriological  study  of  the  pus  in  nineteen  cases  of  empyema ;  in 
only  seven  of  these  could  the  bacillus  of  tuberculosis  be  found ; 
in  the  remaining  twelve  this  microbe  could  not  be  found,  and  upon 
this  negative  ground  the  existence  of  tuberculosis  was  excluded. 
Further  observation  in  these  cases  after  operation  corroborated  the 
diagnosis.  He  asserts,  therefore,  that  in  the  purulent  pleuritic 
exudation  in  tubercular  patients,  in  empyema,  and  pyo-pneumo- 
thorax,  the  presence  of  the  specific-  microbic  cause  can  always  be 
demonstrated.  In  a  case  of  pneumo-hydrothorax  he  failed  to  find 
the  bacillus  until  the  effusion  had  undergone  transformation  into 
pus,  when  its  presence  could  be  readily  demonstrated.  Some  of  the 
pus-corpuscles  contained  as  many  as  twenty  bacilli.  He  places  the 
greatest  importance  on  a  bacteriological  examination  of  the  pus  as  a 


100  SUPPURATION. 

means  of  differential  diagnosis  between  suppurative  and  tubercular 
empyema. 

3.  PURULENT  ARTHRITIS. — Reference  has  already  been  made 
to  the  bacteriological  researches  of  Garre,  who  never  found  bacteria 
of  any  kind  in  the  serous  effusions  of  joints.     Suppurative  syno- 
vitis, in  an  intact  joint,  is  always  caused  by  localization  of  pus- 
microbes  in  the  synovial  membrane,  where  their  presence  excites 
a  purulent  inflammation.     In  this  manner  the  metastatic  suppura- 
tive synovitis,  as  it  occurs  in  pyaemia,  in  some  cases  of  gonorrhoea, 
and  in  some  of  the  general  infective  diseases,  is  caused.     In  ani- 
mals susceptible  to  purulent  infection,  the  injection  into  a  joint  of  a 
pure  culture  of  pus-microbes    is  usually  followed  by  destructive 
purulent  inflammation,  and,  not  infrequently,  by  the  formation  of 
extensive  para-articular  abscesses. 

Hoffa  ("  Bacteriologische  Mittheilungeu  aus  dem  Laboratorium 
der  chirurgischeu  Klinik  des  Prof.  Maas,"  Wiirzburg,  Fortsehritte 
der  Medicin,  B.  iv.  S.  75),  Kranzfeld  ("  Zur  Aetiologie  der  acuten 
Eiterungen,"  St.  Petersburg,  1886,  Centralblatt  f.  Chirurgie,  1886, 
p.  529),  and  Krause  ("  Ueber  acute  eitrige  Synovitis  bei  kleineu 
Kiudern  uud  iiber  den  bei  dieser  Affection  vorkomendeu  Ketten- 
coccus,"  Berl.  klin.  Wochenschrift,  1884,  No.  43)  have  studied  with 
special  care  the  bacteriological  origin  of  suppurating  joints  in  small 
children  a  streptococcus,  the  identity  of  which  with  the  one  de- 
scribed by  Rosenbach  was  proved  by  cultivation  experiments.  In 
one  case  the  same  microbe  was  also  found  in  the  products  of  a  puru- 
lent meningitis,  which  followed  in  the  course  of  the  joint  disease. 
The  same  streptococcus  was  found  by  Heubuer  and  Bahrdt  ("  Zur 
Keuutniss  der  Gelenkeiterung  bei  Seharlach,"  Berl.  klin.  Woehen- 
schrift,  1884,  No.  44)  in  pus  from  a  suppurating  joint,  and  in  the 
diphtheritic  membranes  of  a  scarlet  fever  patient.  Clinical  expe- 
rience and  experimental  research  appear  to  prove  that  purulent 
synovitis  occurring  independently  of  osteomyelitis  is,  in  the 
majority  of  cases,  caused  by  the  streptococcus  pyogenes. 

4.  ACUTE  SUPPURATIVE  OSTEOMYELITIS. — Acute  suppurative 
inflammation  in  bone,  when  it  occurs  independently  of  an  external 
wound,  and  consequently  of  direct  infection,  furnishes  one  of  the 
most  interesting,  and,  thanks  to  the  patient  and  persevering  inves- 
tigations of  a  number  of  the  foremost  pathologists,  one  of  the  best 
known  forms  of  purulent  infection.     For  years  it  has  been  con- 
tended by  some  who  made  the  etiology  of  acute  osteomyelitis  the 
subject  of  experimentation,  that  it  is  caused  by  a  specific  microbe 
not  found  in  other  forms  of  suppuration.     Convincing  evidence, 
however,  has  been  accumulating  for  a  number  of  years  which  seems 
to  leave  no  further  doubt  that  the  ordinary  microbes  of  suppuration 
are  the  cause  of  this  form  of  suppurative  inflammation,  and  that  the 


PUS-MICROBES    IN    SUPPURATIVE    AFFECTIONS.       101 

gravity  of  the  symptoms  which  attend  the  disease,  as  compared  with 
other  suppurative  processes,  is  owing  to  the  anatomical  location  and 
structure  of  the  inflamed  tissues,  rather  than  to  any  difference  in 
the  microbic  cause. 

Rosenbach  (u  Vorlaufige  Mittheilung  iiber  die  acute  Osteomye- 
litis beim  Menschen  erzeugendeu  Microorganismen,"  Centralblatt  f. 
Chirurgie,  1884,  p.  65),  as  early  as  1881,  cultivated  the  staphy- 
lococcus  from  osteomyelitic  pus.  In  one  case  the  yellow  and  the 
white  staphylococcus  were  found  combined,  in  another  case  the 
staphylococcus  albus  alone,  while  in  a  third  case  the  staphylococcus 
aureus  and  the  streptococcus  pyogenes  were  found  present  together. 
Rosenbach  produced  the  same  result  in  his  experiments  by  injection 
of  a  pure  cultivation  of  pus-microbes  from  a  furuncle  of  the  lip,  as 
Struck  did  with  cultivations  from  the  pus  of  osteomyelitis,  and  with 
osteomyelitic  pus  injected  into  the  subcutaneous  connective  tissue  he 
produced  an  ordinary  abscess.  Recurrent  attacks  of  osteomyelitis 
years  after  the  primary  disease,  he  explains  by  assuming  that  after 
the  first  attack  some  of  the  microbes  are  left  in  the  tissues,  and 
remain  in  a  latent  condition  until  at  some  subsequent  time  local 
conditions  are  created  which  enable  them  again  to  display  their 
pathogenic  properties.  Ogston  found  the  staphylococcus  in  the  pus 
of  a  case  of  acute  osteomyelitis. 

Struck  ("  Ueber  eine  im  Kaiserlichen  Gesundheitsamt  ausge- 
fiihrte  Arbeit,  welche  zur  Entdeckung  des  die  acute  infectiose 
Osteomyelitis  erzeugenden  Microorganism  us  gefiihr  that,"  Deutsche 
med.  Wochenschrift,  1883,  No.  46)  obtained  from  the  pus  of  an 
acute  case  of  osteomyelitis  upon  gelatin,  an  orange-yellow  culture; 
the  identity  of  this  cultivation  with  the  staphylococcus  pyogenes 
aureus  was  soon  generally  recognized.  By  injecting  a  pure  culture 
into  the  circulation  of  animals  which  had  been  subjected  a  few  days 
before  to  injury  of  bone,  as  contusion  or  fracture,  he  produced  a 
suppurative  inflammation  at  the  seat  of  trauma. 

Even  before  the  microbic  cause  of  acute  osteomyelitis  was  under- 
stood, Kocher  ("  Die  acute  Osteomyelitis  mit  besouderer  Riicksicht 
auf  ihre  Ursachen,"  Deutsche  Zeitschrift  /.  Chirurgie,  B.  xi.  S.  87) 
believed  that  the  infection,  in  some  cases  at  least,  occurred  through 
the  intestinal  canal,  and  made  some  experiments  to  prove  this  point. 
In  dogs  he  produced  subcutaneous  fractures,  and  then  fed  them 
large  quantities  of  putrid  material,  and,  in  some  cases,  succeeded  in 
producing  suppuration  at  the  seat  of  injury.  In  his  clinical  expe- 
rience he  also  observed  that  in  many  cases  of  acute  suppurative 
osteomyelitis  the  premonitory  symptoms  pointed  to  the  gastro- 
intestinal canal  as  the  portio  invasionis. 

Krause  ("  Ueber  einen  bei  der  acuten  infectiosen  Osteomyelitis  des 
Meuschen  vorkommenden  Mierococcus,"  Fortschritte  der  Medicin, 


102  SUPPUKATION. 

1884,  Xos.  7,  8)  cultivated  from  osteomyelitic  pus  the  stapbylococcus 
pyogenes  aureus  aud  albus,  which  he  also  found  in  the  effusion  iu 
joints,  when  this  occurred  as  a  complication  of  the  disease.  Injec- 
tion of  a  pure  culture  of  these  cocci  into  the  peritoneal  cavity  of 
animals  caused  suppurative  peritonitis.  Intravenous  injections, 
with  or  without  previous  fracture,  were  followed  most  frequently 
by  suppuration  in  joints  and  muscles.  If  a  bone  was  fractured 
subcutaneously  before  the  injection,  he  frequently  observed  suppu- 
ration at  the  seat  of  fracture,  and  from  the  pus  the  staphylococcus 
could  again  be  cultivated.  Foci  in  the  kidneys  were  always  present 
in  all  of  these  experiments. 

Garre  ("Zur  Aetiologieacuteitriger  Entziinduugen,"  Fortscliritte 
der  Jle<iicm,1885,  p.  165)  corroborated  by  his  own  experimental 
work  the  observations  made  by  Rosenbach,  and,  in  addition,  he 
showed  that  in  acute  suppurative  osteomyelitis  the  staphylococcus 
is  also  present  in  the  blood. 

Miiller  ("  Die  acute  Osteomyelitis  der  Geleukgebiete,"  Deutsche 
Zeitschrift  /.  Chirurgie,  B.  xxi.  Hefte  5  u.  6)  succeeded  in  cultivating 
the  staphylococcus  pyogenes  aureus  from  the  yellow  granulations  iu 
cases  of  acute  epiphysary  osteomyelitis. 

Rodet's  ("  Etude  experimentelle  sur  P  osteomyelite  iufectieuse," 
Compt.  rend.,  1884,  No.  14)  researches  deserve  special  mention,  as  he 
succeeded  in  producing  suppurative  osteomyelitis  in  animals  without 
inflicting  a  trauma  before  or  after  the  infection.  This  result  could 
only  be  obtained  by  resorting  to  intravenous  injections.  The  puru- 
lent inflammation,  which  was  generally  circumscribed,  was  usually 
located  near  the  epiphysis ;  it  seldom  extended  over  a  considerable 
portion  of  the  shaft.  In  many  cases  epiphyseolysis  occurred,  and 
very  frequently  a  suppurative  arthritis  of  the  adjacent  joint.  In 
the  most  acute  cases,  the  animals  died  within  twenty- four  hours 
without  any  appreciable  changes  in  the  bones.  The  detection  of 
the  microbes  in  the  blood  was  the  most  difficult ;  they  were  found 
most  readily  in  the  kidneys,  in  which  often  multiple  abscesses  were 
found.  Subcutaneous  inoculation  resulted  in  local  suppuration ; 
osteomyelitis  could  not  be  produced  in  this  manner.  Young  ani- 
mals were  more  susceptible  to  inoculations.  According  to  Rodet, 
the  osteomyelitic  cultures  lose  their  virulence  after  thirty  to  forty 
days.  In  one  of  his  experiments,  which  he  details  very  minutely, 
he  employed  a  culture  of  the  thirteenth  generation,  and  produced 
epiphyseal  osteomyelitis  of  both  femora,  of  one  tibia,  and  of  one 
humerus.  As  the  result  of  his  observations,  he  locates  as  the 
primary  seat  of  osteomyelitis  of  the  long  bones  the  medulla  in  close 
proximity  to  the  epiphyseal  line.  When  separation  of  the  epiphy- 
sis was  observed,  the  pathological  fracture  always  occurred  on  the 
side  of  the  diaphysis. 


PUS-MICROBES    IX    SUPPURATIVE    AFFECTIONS.       103 

Ribbert  ("  Die  Schicksale  der  Osteomyelitis-coccen  im  Organis- 
rnus,"  Deutsche  med.  Woehenschrift,  1884,  No.  24)  made  investiga- 
tions to  ascertain  the  extent  of  diffusion  of  the  osteomyelitic  cocci 
in  the  organism.  Twenty-four  hours  after  direct  injection  into  the 
circulation  he  found  them  in  all  the  organs,  later  only  in  the  kid- 
neys. In  regard  to  their  localization,  the  following  conditions  must 
be  taken  into  consideration  : 

a.  Embolic  obstruction  of  capillary  vessels. 

b.  Elimination  of  pus-microbes  through  the  kidneys. 

c.  The  influence  of  traumatism. 

Liibbert  (Biologische  Spaltpilzimtersuchung.  Der  Staphylococcus 
pyogenes  aureus  und  der  Osteomyelitis-coccus.  "Wiirzburg,  1886) 
has  studied  the  effect  of  the  staphylococcus  pyogenes  aureus,  the 
microbe  most  frequently  found  in  osteomyelitis  in  the  different 
tissues.  From  his  experiments  he  came  to  the  conclusion  that  the 
intensity  of  its  action  varies  greatly  without  a  sufficient  cause  for  it 
being  known.  Inoculations  with  it  of  superficial  abrasions  pro- 
duced no  effect.  Subcutaneous  inoculations  resulted  in  the  forma- 
tion of  abscesses  which  at  times  became  quite  diffuse.  Inoculations 
of  granulation  surfaces  proved  harmless.  Injections  into  the  pleural 
and  peritoneal  cavities  were  oftenest  followed  by  intense  general 
symptoms.  Injections  into  the  trachea  through  a  tracheotomy 
wound  produced  suppurative  tracheitis  and  foci  in  the  lungs.  In- 
travascular  injections  were  followed  by  symptoms  indicative  of 
sepsis.  Foci  were  also  found  in  the  intestinal  mucous  membrane. 
Feeding  experiments  proved  harmless. 

Kraske  ("  Zur  Aetiologie  und  Pathogenese  der  acuteu  Osteomye- 
litis," Arehivf.  Idin.  Chirurgie,  B.  xxxiv.  S.  701)  has  studied  from 
a  clinical  standpoint,  the  manner  of  infection  in  cases  of  acute  osteo- 
myelitis. In  one  case  he  could  trace  the  infection  distinctly  to  a 
furuncle  of  the  lip ;  but,  as  a  rule,  he  thinks  that  infection  takes 
place  through  a  wound  or  abrasion  of  the  skin.  Infection  through 
the  intestinal  canal  he  considers  possible,  but  not  proven  ;  more 
frequently  it  takes  place  through  the  respiratory  organs,  and  in  one 
case  he  could  locate  the  infection  here  with  certainty.  He  asserts 
that  recurring  attacks  should  not  always  be  looked  upon  as  the 
result  of  former  infection,  but  as  a  consequence  of  a  new  infection. 
He  formulates  the  result  of  his  clinical  studies  as  follows : 

a.  The  staphylococcus  pyogenes  aureus  can  produce  osteomyelitis, 
and,  in  fact,  is  most  frequently  met  with  in  the  osteomyelitic  pro- 
ducts. 

6.  In  a  certain  number  of  cases  acute  osteomyelitis  is  the  result 
of  a  mixed  infection  and  is  then  most  prone  to  pursue  a  severe 
course. 

c.  It  is  possible  that  the  result  of  further  investigation  will  show 


104  SUPPURATION. 

that  every  microorganism  that  possesses  pyogenic  properties  is  capa- 
ble of  causing  a  typical  osteomyelitis  in  man. 

Rinne  ("  Ber  Eiterungsprocess  und  seine  Metastasen,"  Archiv 
fur  klin.  Chirurgie,  B.  xxxix.  S.  21),  who  failed  in  producing  metas- 
tatic  abscesses  with  pure  cultures  of  pus-microbes,  rendered  four 
rabbits  pysemic  by  injecting  osteomyelitic  pus  directly  into  the 
venous  circulation.  He  used  pus  later  from  a  case  of  acute  osteomye- 
litis with  grave  symptoms,  and  diluted  it  with  distilled  water,  and 
of  such  a  mixture  he  injected  a  syringeful  into  one  of  the  auricular 
veins  of  four  rabbits.  One  died  in  twenty-four  hours  with  symp- 
toms of  toxaemia,  and  the  autopsy  showed  nothing  but  a  beginning 
pneumonia  of  the  left  lung.  The  other  three  animals  died  seven  to 
ten  days  after  the  injection,  and  in  all  of  them  the  necropsy  showed 
suppurating  foci  in  the  kidneys  and  the  heart  muscle.  No  abscesses 
in  muscles  or  suppuration  in  joints.  The  plate  cultures  made  from 
the  pus  used  for  the  experiments  showed  the  staphylococcus  aureus 
albus  and  bacillus  pyocyaneus.  With  the  exception  of  the  albus, 
all  of  the  microbes  were  also  cultivated  from  the  pus  of  the  metas- 
tatic  abscesses  in  rabbits. 

In  a  later  examination  (Ibid.,  p.  271)  the  same  author  expresses 
the  opinion  that  the  indirect  causes  of  suppurative  osteomyelitis  are 
changes  brought  about  in  the  medullary  tissue  by  the  microbes  and 
their  ptomaines  of  general  febrile  diseases,  such  as  typhus,  scarla- 
tina, diphtheria,  etc.,  which  prepare  the  soil  for  the  action  of  pus- 
microbes,  or  the  disease  is  produced  by  direct  extension  from  a 
localized  suppurative  lesion,  as  a  furuncle,  through  lymphatic  vessels 
or  along  vessel  sheaths  or  nerve  trunk  to  the  medullary  tissue. 

The  structure  and  location  of  the  capillary  vessels  in  the  vicinity 
of  the  epiphyseal  cartilage  in  young  persons  determine  the  localiza- 
tion of  pus-microbes  in  this  part  of  the  long  bones,  and,  almost 
without  exception,  the  inflammatory  process  starts  from  here. 

The  rapid  local  diffusion  of  the  process  is  largely  due  to  the 
unyielding  nature  of  the  tissues  around  the  primary  focus,  and  to 
the  fact  that  the  bloodvessels  are  directly  concerned  in  the  exten 
sion  of  the  process  by  becoming  the  channels  for  the  dissemination, 
their  contents  forming  the  nutrient  medium  for  the  pus-microbes. 
Thrombo-phlebitis  is  a  constant  and  early  condition  in  every  case 
of  acute  osteomyelitis.  Coagulated  blood  is  an  excellent  culture 
substance  for  the  pus-microbes,  and  it  serves  the  double  purpose  of 
a  nutrient  substance,  and  a  medium  for  the  local  spread  of  the  dis- 
ease. General  dissemination  and  metastatic  foci  in  distant  organs, 
or  in  other  bones,  are  often  observed  because  the  pus-microbes 
re-enter  the  vascular  system  again,  and  by  so  doing  cause  a  coagu- 
lation-necrosis of  the  intima  and  thrombosis;  and  subsequently 


PUS-MICKOBES    IN    SUPPUEATIVE    AFFECTIOXS.       105 

intravascular  growth  and  general  dissemination  from  such  centres 
of  germ  growth  take  place. 

In  some  cases  even  during  the  earliest  stages  the  general  symp- 
toms are  out  of  all  proportion  to  the  local  lesion,  presenting  a  clini- 
cal picture  characteristic  of  intense  septic  intoxication.  It  is  very 
possible  that  the  ptomaines  produced  by  the  pus-microbes  in  the 
medullary  tissue  of  bone  may  be  more  virulent  or  produced  in 
larger  quantities  than  in  suppurative  inflammations  in  other  organs. 
Again,  the  ptomaines  gain  here  more  ready  entrance  into  the  circu- 
lation, as,  at  least,  part  of  them  are  produced  within  the  bloodvessels 
and  the  extravascular  products  are  forced  rapidly  into  the  circula- 
tion on  account  of  the  unyielding  nature  of  the  tissues  around  the 
primary  focus  of  inflammation. 


CHAPTEE   IX. 

GANGRENE. 

GANGRENE,  resulting  from  mycosis  of  the  tissues,  is  caused  by 
oue  of  three  well  defined  conditions  : 

1.  The  microbes  are  so  numerous  in  the  capillary  vessels  that 
their  presence  interferes  mechanically  with  the  blood  supply,  and 
death  of  the  part  ensues  in  consequence  of  greatly  diminished  or 
suspended  nutrition. 

2.  The  microbes  in  the  tissues  produce  ptomaines  which  destroy 
the  tissue  by  their  direct  destructive  chemical  action  on  the  proto- 
plasm of  the  cells. 

3.  The  specific  inflammation  caused  by  the  microbic  infection  is  so 
intense  that  the  inflammatory  products  in  the  paravascular  tissues 
accumulate  so  rapidly,  and  in  such  abundance,  that  nutrition  is  sus- 
pended by  impairment  or  suspension  of  the  arterial  blood  supply  or 
mechanical  interference  with  the  venous  return  of  the  blood  from 
the  part,  or  both  of  these  conditions  combined. 

For  these  reasons  no  one  variety  of  microbes  can  be  the  sole  cause 
of  gangrene.  In  its  different  forms,  different  microbes  will  be 
found.  In  cases  of  inoculation  anthrax,  when  at  the  point  of  in- 
oculation an  abundant  growth  of  the  bacillus  takes  place,  the  con- 
nective-tissue spaces  and  bloodvessels  become  so  blocked  with  the 
bacilli  that  circulation  is  mechanically  arrested,  and  a  circumscribed 
gangrene  is  the  result.  In  the  progressive  gangrene  which  Koch 
produced  artificially  in  rabbits  by  subcutaneous  inoculation  of  putrid 
fluids,  the  gangrene  always  occurred  in  advance  of  the  line  of  mi- 
crobic invasion,  and  must,  on  that  account,  have  been  caused  by 
the  local  toxic  effects  of  the  ptomaines.  In  phlegmonous  inflam- 
mation, when  the  process  is  very  acute  and  diffuse,  gangrene  fre- 
quently follows  as  one  of  the  consequences  of  the  inflammation,  and 
the  microbe  which  is  found  in  the  gangrenous  part  is  the  same  as 
that  which  caused  the  inflammauitiou. 

Tricomi  ("  II  micro-parasitica  della  gangrena  senile,"  Rivista 
internazionale  di  Medicina  e.  CMrwgia,  1886)  has  found  a  slender, 
long  bacillus  in  the  blood  of  patients  suffering  from  senile  gangrene. 
The  same  bacillus  was  also  found  in  the  secretions  of  the  gangrenous 
part  at  the  line  of  demarcation  in  the  lymph  spaces  and  in  the  sub- 
cutaneous connective  tissue  beyond  the  seat  of  gangrene.  He  culti- 


GAXGKENE.  107 

vated  the  microbe  successfully  upon  gelatin,  agar-agar,  blood  serum, 
and  potato.  The  bacillus  was  readily  stained  with  red  and  blue 
aniline  dyes,  and  often  a  spore  could  be  seen  either  at  one  of  its 
extremities  or  near  its  centre.  Injection  of  one-half  to  one  gramme 
of  a  pure  culture  grown  upon  gelatin  was  injected  under  the  skin 
over  the  back  of  a  guinea-pig,  house-mouse,  or  rabbit,  and  death 
was  produced  in  from  two  to  three  days.  A  form  of  gangrene 
resembling  senile  gangrene  was  always  found  at  the  point  of  inocu- 
lation, but  no  changes  in  the  blood  or  other  organs  were  observed. 
Gangrene  could  also  be  produced  in  other  animals  by  inoculating 
the  secretions  from  the  gangrenous  part.  The  researches  of  Arloing 
and  Chaveau  are  of  the  greatest  importance  in  the  elucidation  of  the 
etiology  of  gangrene  as  it  is  sometimes  observed  in  connection  with 
septic  infection.  These  observers  have  published  the  results  of 
some  recent  investigations  on  the  pathology  and  prophylaxis  of 
gangrenous  or  gaseous  septicaemia  of  man.  It  is  the  prevailing 
opinion  that  this  disease  is  a  surgical  complication,  of  which  the  ex- 
clusive cause  is  the  introduction  of  a  specific  microbe  into  a  wound. 
In  man  the  microbe  exists  in  the  connective  tissue  which  surrounds 
the  wound,  and  in  the  contents  of  bullse,  which  may  be  developed 
in  its  neighborhood.  The  microbe  is  a  short,  thick,  mobile  rod,  of 
homogeneous  structure,  or  else  provided  with  one  spore,  rarely  two, 
at  one  of  the  extremities.  When  the  bacillus  appears  in  the  blood 
at  the  end  of  this  disease,  and  sometimes  only  after  death,  its  size  is 
smaller  than  in  the  local  lesion,  and  it  may  appear  in  the  form  of  a 
micrococcus.  A  number  of  animals,  such  as  the  horse,  ass,  sheep, 
pig,  dog,  cat,  guinea-pig,  white  rat,  rabbit,  duck,  and  other  fowls, 
have  been  successfully  inoculated,  but  the  rabbit  is  not  very  sus- 
ceptible to  this  disease,  in  this  respect  presenting  a  marked  contrast 
with  another  form  of  septicaemia.  The  most  prompt  way  of  pro- 
ducing the  disease  was  found  to  be  by  subcutaneous  injection.  The 
smallest  dose  capable  of  causing  death  when  injected  into  the  con- 
nective tissue,  never  proved  fatal  when  injected  into  the  veins  or 
arteries ;  in  the  latter  case,  only  a  temporary  intoxication  was  pro- 
duced. If  a  large  dose  was  injected  into  a  vein,  death  ensued,  with 
well-marked  septic  infection  of  the  serous  membranes.  It  was 
found  difficult,  if  not  impossible,  to  produce  the  disease  by  feeding- 
experiments.  Attempts  to  inoculate  a  healthy  wound  involving 
the  skin,  connective  tissue,  and  muscles  were  unsuccessful.  On 
the  contrary,  the  microbes  of  this  disease  find  a  favorable  soil  in 
dead  tissues  not  exposed  to  air.  Protection  from  the  disease  is 
afforded  in  sheep  and  dogs  by  the  successive  injection  of  two  or 
three  moderate  doses  of  the  virus  into  the  circulation.  Inoculation 
into  the  subcutaneous  connective  tissue  of  animals  thus  protected, 
gave  rise  to  a  simple  circumscribed  phlegmonous  inflammation 


108  GANGRENE. 

which  ran  its  course  in  eight  days.  The  pus  from  such  an  abscess 
may  contain  the  specific  microbe,  and  may  act  as  the  original  virus. 
Experiments  showed  that  this  disease  could  be  transmitted  from 
mother  to  foatus.  The  bacillus  could  be  destroyed  by  heat  alone  if 
exposed  to  a  temperature  from  90°  to  100°  C.  (194°  to  212°  F.) 
for  a  quarter  of  an  hour.  In  the  dried  state  the  virus  is  extremely 
resistant.  However,  it  can  be  destroyed  after  immersion  in  a  hot 
bath  (120°  C.,  248°  F.)  in  from  ten  to  fifteen  minutes.  There  can 
be  no  doubt  that  the  bacillus  described  here  is  a  saprophyte,  and 
that  it  is  identical  with  one  of  the  bacilli  saprogenes  described  by 
Rosen  bach. 

Brigadier- Surgeon  Godwin  (British,  Medical  Journal,  July  23, 

1887)  reports  a  case  of  progressive  gangrene  with   emphysema, 
starting  from  an  inflamed  corn,  which  extended  with  such  rapidity 
that  a  week  after  it  commenced  it  had  extended  so  high  as  to  neces- 
sitate amputation  in  the  thigh.    The  man  suffered  from  grave  septic 
intoxication,  the  symptoms  of  which  persisted  for  a  number  of  days 
after  the  amputation,  until  the  ptomaines,  had   been   eliminated. 
Culture  experiments  with  the  pus  showed  the  presence  of  strepto- 
coccus pyogenes  and  staphylococcus  pyogenes  albus. 

William  Koch  ("  Milzbrand  u.  Rauschbrand,"  Deutsche  Chi- 
rurgie,  Lieferung  9)  states  that  in  a  case  of  progressive  gangrene 
with  emphysema  in  a  young  man,  he  found  a  bacillus  which  resem- 
bled the  bacillus  of  glanders,  and  proved  its  identity  by  cultivation 
and  inoculation  experiments. 

Ciarrocchi  (Yirchow  u.   Hirsch's  Jahresbericht,  B.  xi.   S.  642, 

1888)  describes  a  case  of  rnetastatic  gangrene  of  the  skin,  caused  by 
infection  through  a  lacerated  wound  of  the  last  phalanx  of  the  little 
finger.     Ten  days  after  the  accident  the  patient  became  ill,  com- 
plaining of  chilly  sensations,  which  were  followed  by  fever  and 
thirst.     The  next  day  yellowish-white  spots  appeared  on  the  chest, 
which   were   diagnosticated  as  gangrseua  cutauea.      Suspecting  a 
causal  relation  between  the  injured  finger  and  the  gangrene  of  the 
skin,  cultures  were  made  from  the  necrotic  tissue  upon  gelatin  and 
the  following    microbes  were   isolated :    staphylococcus   pyogenes 
aureus,  staphylococcus  cereus  albus,  and  a  brown  culture  in  which 
a  short  bacillus  was  found.     Inoculation  experiments  could  not  be 
made  as  the  material  was  lost,  but  the  results  of  the  microscopical 
examination  agreed  with  those  of  Demme,  which  he  obtained  from 
gangrenous  spots  in  the  skin  of  five  children  affected  with  erythema 
nodosa.     The  latter  observer  also  isolated  the  two  varieties  of  pus- 
microbes  and  a  short,  fine  bacillus,     This  bacillus,  when  injected 
under  the  skin  of  animals,  produced  gangrenous  spots  and  a  nodular 
efflorescence. 

Jaffe  and  Leydeu  (Deutsches  Archivf.  klin.  Medicin,  B.  ii.  S.  488) 


GANGRENE.  109 

found  leptothrix  threads  in  gangrenous  foci  of  the  lung,  and  attrib- 
uted to  them  the  cause  of  the  gangrene ;  but  their  presence  only 
proved  the  possibility  of  the  entrance  of  foreign  bodies  from  the 
mouth  into  the  lungs,  and,  while  they  played  no  essential  part  in 
the  causation  of  the  gangrene,  the  observation  shows  in  what  way 
other  and  more  deleterious  microorganisms  can  enter  the  lungs  with 
the  air  through  the  bronchial  tubes. 

Bonome  (Deutsche  med.  Wochenschrift,  1886,  No.  52)  examined 
nine  cases  of  gangrene  of  the  lungs  in  man,  and  found  in  three  of 
them  staphylococcus  pyogeues  aureus  alone ;  in  five  staphylococcus 
pyogenes  alone,  and  in  one  both  microbes  together.  He  made  a 
number  of  experiments  for  the  purpose  of  producing  gangrene  in 
the  lungs  of  rabbits,  by  injecting  pus-microbes  into  the  circulation, 
but  the  results  were  negative  if  only  the  cultivations  were  used.  He 
obtained  positive  results  by  mixing  with  the  cultivations  particles 
of  the  pith  of  elder,  and  injecting  this  mixture  into  the  jugular 
vein.  The  result  was  multiple  small  abscesses,  and  gangrene  of 
the  lung.  Injection  of  the  pith  fragments  alone  caused  no  effect. 
The  pith  fragments  in  these  experiments  determined  an  intense 
inflammation  in  the  peri-bronchial  tissues  by  causing  alteration  of 
tissue,  thus  preparing  the  soil  for  the  localization  and  pathogenic 
action  of  the  pus-microbes.  The  gangrene  of  the  lung  in  man  does 
not  follow  in  consequence  of  the  croupous  inflammation  caused  by 
the  pneumococcus,  but  its  occurrence  indicates  that  secondary  infec- 
tion has  taken  place  with  one  or  more  varieties  of  pus-microbes,  or 
with  saprophytes. 

In  compound  fractures  of  the  limbs  by  direct  violence,  gangrene, 
with  or  without  emphysema,  is  a  comparatively  frequent  complica- 
tion when  infection  takes  place,  as  the  death  of  the  tissues  from  the 
trauma,  and  the  nature  of  the  wound,  furnish  the  most  favorable 
conditions  for  the  growth  of  pus-microbes  and  the  bacilli  of  putre- 
faction. 


CHAPTER    X. 

SEPTICAEMIA. 

SEPTIC  processes  were  among  the  first  to  excite  interest  in  the 
part  played  by  microorganisms  in  disease,  and  it  is  due  to  this  fact 
that  so  much  more  has  been  said  and  written  on  septicaemia  than 
on  any  other  microbic  disease  in  surgery.  Although  some  of  the 
best  pathologists  have  been  diligently  investigating  this  subject  for 
years,  we  still  remain  in  the  dark  concerning  its  true  etiology,  and 
its  relation  to  other  infective  processes.  True  sepsis  is  looked  upon 
as  a  general  infection  from  some  local  source,  unattended  by  any 
gross  pathological  changes.  Some  writers  have  claimed  the  differ- 
ence between  septicaemia  and  pyaemia  to  be  a  quantitative  and  not  a 
qualitative  one,  while  others  maintained  that  pyaemia  was  a  specific 
disease  sui  generis,  and  that  it  was  in  nowise  related  to  sepsis. 
They  resemble  each  other  so  far,  that  both  are  caused  by  micro- 
organisms. 

HISTORY. — The  first  reliable  investigations  into  the  microbic 
origin  of  sepsis  were  made  by  Rindfleisch  in  1866,  and  somewhat 
later  by  Klebs,  Recklinghausen,  Waldeyer,  and  Hueter.  Rindfleisch 
found  bacteria  in  abscesses,  while  the  researches  of  Klebs  (^Beitrdge 
zur  pathol.  Anatomie  der  Sehussu-unden,  Leipzig,  1872)  initiated  a 
new  era  in  the  etiology  of  septic  diseases.  The  latter  author  diifer- 
entiated  between  septicaemia  and  pyaemia,  although  he  claimed  that 
putrid  and  septic  infection  were  the  same.  He  found  in  the  tissues 
altered  by  septic  processes,  also  in  the  lymph  spaces  and  in  the 
blood,  a  microbe,  a  round  coccus,  isolated  and  in  groups,  which  he 
termed  mikrosporon  septicum.  Rosen  bach  (Microorganismen  bei  den 
Wound-infections  Krankheiten  des  Menschen,  Wiesbaden,  1884)  in 
three  cases  of  septicaemia  which  he  subjected  to  bacteriological  ex- 
amination, found  the  staphylococcus  pyogenes  aureus  present  each 
time  in  the  pus;  in  two  of  these  cases  he  isolated  and  cultivated 
from  the  products  of  septic  inflammation  the  bacillus  saprogenes. 
In  two  of  the  cases  no  cultivation  could  be  obtained  from  the  blood. 
In  two  cases  of  gangrene,  with  general  septicaemic  symptoms,  the 
microbe  found  was  the  streptococcus  pyogenes.  Intoxication  symp- 
toms from  the  introduction  of  putrid  material,  he  attributed  to  the 
presence  of  one  or  more  varieties  of  the  bacillus  saprogenes,  which 
he  designates,  respectively,  Nos.  1,  2,  3.  No.  1  he  cultivated  from 


HISTORY.  Ill 

putrid  blood,  and  this  he  believes  to  be  quite  harmless,  while  the 
remaining  two  possess  pyogenic  properties. 

No.  1.  Large  rods,  which,  cultivated  on  nutrient  agar-agar,  form 
an  irregular  sinuous  streak,  with  a  mucilaginous  appearance.  They 
grow  also  very  readily  on  blood-serum,  and  all  cultivations  yield 
the  odor  of  rotting  kitchen-refuse.  It  is  not  pathogenic. 

No.  2.  Rods  shorter  and  thinner  than  No.  1.  They  develop 
very  rapidly  on  agar-agar,  forming  transparent  drops,  which  be- 
come gray.  They  were  isolated  from  a  patient  suffering  from  pro- 
fusely sweating  feet.  The  cultivations  yielded  a  characteristic  odor 
similar  to  the  last.  They  are  pathogenic. 

No.  3.  Hods  isolated  from  the  putrid  marrow  of  a  case  of  com- 
pound fracture,  cultivated  on  agar-agar ;  an  ash-gray,  almost  liquid 
culture  is  developed,  with  a  strong  characteristic  odor  of  putrefac- 
tion. Injected  into  the  knee-joint  or  abdomen  of  a  rabbit,  they 
cause  snppurative  inflammation. 

According  to  Chaveau  (u  Septicemie  gangreneuse,"  Publ.  de 
I'Acad.  de  Med.,  No.  34, 1884),  the  microbe  of  septicaemia  is  iden- 
tical with  the  vibrion  septique  described  by  Pasteur.  Both  of  these 
authors  claim  that  this  microbe  is  anaerobic,  and  Chaveau  only 
succeeded  in  cultivating  it  in  a  vacuum.  He  made  many  experi- 
ments on  guinea-pigs,  sheep,  and  horses,  by  injecting  the  liquid 
contents  of  bullae  which  he  found  in  cases  of  septic  gangrene.  In 
doses  of  one-fifth  of  a  drop  in  guinea-pigs,  and  from  two  to  four 
drops  in  horses,  it  produced  rapid  death.  In  all  cases  the  necropsy 
showed  at  the  point  of  injection  localized  oedema  and  turbid  serum 
in  the  peritoneal,  pleura!,  and  pericardial  cavities.  In  the  fluids, 
the  microbe  could  always  be  demonstrated  under  the  microscope. 
The  disease  could  be  reproduced  in  other  animals  by  inoculation 
with  the  serous  fluid  contained  in  any  of  the  serous  cavities.  The 
microbe  proved  less  virulent  when  injected  directly  into  the  circu- 
lation. All  animals  which  recovered  after  intravenous  injection 
were  protected  against  any  further  subcutaneous  inoculations. 

Gautier  and  others  have  more  abundantly  proved  that  not  only 
after  death,  but  even  during  life,  the  animal  organism,  by  virtue  of 
its  physiological  powers,  is  able  to  elaborate  the  alkaloids  to  which 
the  name  of  leucoma'ines  has  been  applied,  bodies  which  are,  many 
of  them,  essentially  toxic  in  their  properties,  and  which  resemble  so 
closely  the  poisonous  cadaveric  alkaloids  to  which  Selmi  first  called 
attention. 

Watson  Cheyne  ("  Report  on  Micrococci  in  Relation  to  Wounds, 
Abscesses,  and  Septic  Processes,"  British  MedicalJournal,  1884,  pp. 
553,  559,  645)  asserts  that  the  microbes  of  sepsis  only  grow  in  loco, 
and  act  by  producing  toxic  ptomaines,  or  if  they  occur  in  the  blood, 


112  SEPTICAEMIA. 

they  do  not  make  emboli ;  they  are  not  always  cocci,  sometimes 
rods. 

At  the  last  meeting  of  the  German  Medical  Congress  (Berl.  klin. 
Woohensehrift,  1888,  No.  18)  Jiirgensen  read  a  paper  on  krypto- 
genetic  septico-pysemia,  in  which  he  referred  to  100  cases  of  this 
disease  which  had  come  under  his  own  personal  observation,  and 
in  which  it  was  impossible  to  locate  the  source  of  infection.  The 
microbes  found  were  either  streptococci  or  staphylococci,  or  both 
together,  in  the  same  patient.  He  stated  that  the  streptococcus 
circulated  in  the  blood,  while  the  staphylococcus  produced  local 
processes. 

Yidal  (Gf-az.  hebdom.,  No.  22,  1888)  has  reported  to  the  Acade- 
mic de  Medecine  de  Paris  the  results  of  his  studies  of  the  "forme 
septicemique  pure "  in  puerperal  fever,  of  •  typhoid  type  without 
suppuration.  In  all  of  his  cases  he  found  the  streptococcus  pyo- 
genes,  and  from  this,  and  the  result  of  his  culture  and  inoculation 
experiments,  he  comes  to  the  conclusion  that  it  is  impossible,  in  the 
present  state  of  our  knowledge,  to  distinguish  between  the  various 
forms  of  streptococci,  and  that  one  and  the  same  form  can  set  up 
any  of  the  various  forms  of  puerperal  infection. 

Besser  (St  Louis  Medical  and  Surgical  Journal,  1888,  No.  2) 
states  that  he  has  examined  22  additional  cases  of  traumatic  septi- 
caemia, and  found  streptococcus  in  every  one  of  them.  During  the 
patient's  life  he  discovered  the  microbe  (a)  in  blood,  in  4  of  1 6 
cases  examined ;  (6)  in  pus  or  fluid  discharge  from  the  primary 
focus,  in  17  of  17 ;  (c)  in  urine,  in  3  of  4,  and  (d)  in  sputa,  in  3  of 
3 ;  while  after  death  the  microorganism  was  present  (a)  in  blood, 
in  7  of  15  ;  (b)  in  organs,  in  16  of  18  ;  and  (c)  in  pus  or  uterine 
discharges,  in  12  of  12.  In  6  of  22  staphylococci  were  simul- 
taneously detected,  side  by  side  with  masses  of  bacteria  of  many 
other  species.  In  3  cases,  however,  the  streptococcus  alone  could 
be  found.  The  author  supposes  that  septicaemia  is  produced  solely 
by  the  streptococcus.  The  microbe  itself  penetrates  into  the 
organism  but  very  seldom. 

From  the  above  historical  consideration  it  becomes  evident  that 
the  essential  cause  of  septicaemia  has  as  yet  not  been  demonstrated. 
The  streptococcus  pyogeues  has  been  found  most  frequently  in  the 
products  of  septic  inflammations,  but  whether  any  of  the  pus- 
microbes  alone  are  capable  of  producing  true  sepsis  remains  to  be 
demonstrated  by  future  research.  As  the  introduction  into  the 
circulation  of  the  products  of  putrefaction  is  followed  by  a  corn- 
plexus  of  symptoms  which  closely  resemble  septicaemia,  and  as  dif- 
ferent microbes  have  been  cultivated  from  septic  patients,  it  would 
seem  that  this  disease  can  be  produced  by  any  of  the  microbes 
which,  after  their  introduction  into  the  organism,  have  the  capacity 


PLATE    III. 


Micrococcus  growth  in  the  capillaries  of  the  lungs  in  a  case  of 
puerperal  sepsis,  after  septic  thrombosis  of  the  internal  spermatic  vein. 

a.  Filling  the  capillaries. 

b.  Rupture  of  one  of  them. 


ARTIFICIAL    SEPTICAEMIA    IX    AXIMALS.  113 

to  produce  a  sufficient  quantity  of  poisonous  ptomaines  to  give  rise 
to  progressive  septic  intoxication. 

ARTIFICIAL  SEPTICAEMIA  IN  AXIMALS. — In  the  latter  part  of 
the  seventeenth  century,  Kircher  and  Leuweuhoek  claimed  that 
putrid  substances  contained  minute  microscopical  worms  which 
caused  the  putrefaction.  Perty  and  Naegeli  assigned  to  the  minute 
organisms  a  vegetable  origin  instead  of  animalculae,  as  had  been 
previously  done,  and  they  were  classified  under  the  name  of  schizo- 
mycetes.  In  1857,  Pasteur  made  the  important  discovery  that 
specific  agents  are  the  cause  of  the  various  forms  of  fermentation 
and  putrefaction.  No  discovery,  perhaps,  attracted  such  universal 
and  deep  attention  as  Pasteur's  theory  of  fermentation.  This 
theory  was  strengthened  somewhat  later  by  Lemaire's  observa- 
tion, that  all  fermentative  changes  in  fluids  are  suspended  on  the 
addition  to  the  fluids  of  pheuic  acid,  from  which  he  concluded  that 
fermentation  must  be  due  to  living  organisms.  As  for  a  long  time 
all  septic  affections  were  supposed  to  be  caused  by  a  process  of  fer- 
mentation and  putrefaction,  these  theories  led  to  a  diligent  search 
for  microorganisms  in  the  fluids  of  septic  patients,  and  to  experi- 
mentation on  animals  with  putrid  substances.  Koch,  in  his  great 
work  on  wound-infective  diseases,  published  in  1878,  described 
two  distinct  varieties  of  septicaemia,  one  in  mice  and  the  other  in 
rabbits.  In  fifty-four  infected  mice  he  found  small  bacilli  in  the 
interior  of  the  white  blood-corpuscles,  and  also  in  the  capillaries 
after  they  were  set  free  by  the  destruction  of  the  blood-corpuscles. 
They  were  also  found  in  the  serous  cavities  and  in  the  lymphatic 
glands  and  vessels.  The  bacillus  of  mouse  septicaemia  was  found 
very  difficult  to  cultivate,  and  Koch  .first  succeeded  in  cultivating 
it  upon  a  composition  of  gelatin  with  the  aqueous  humor  of  the 
eye  of  the  ox.  The  growth,  however,  was  very  feeble,  and  succes- 
sive cultivations  upon  the  same  soil  were  uncertain.  Later,  Loef- 
fler  succeeded  better  with  a  nutrient  medium  composed  of  infusion 
of  meat,  to  which  were  added  1  per  cent,  of  peptone  and  0.6  per 
cent,  of  common  salt,  the  whole  rendered  faintly  alkaline  with 
sodium  phosphate.  The  bacilli  appeared  upon  this  clear  and 
transparent  soil  as  opacities  upon  its  surface.  In  rabbits  he  found 
large  oval  micrococci  free  in  the  capillaries.  The  progressive 
character  of  septicaemia  was  well  shown  by  Koch  and  Davaine  in 
rabbits,  as  the  latter  could  cause  rapid  death  by  injecting  a  single 
drop  of  a  mixture  prepared  by  adding  to  a  quantity  of  blood  of  a 
rabbit  which  had  died  inoculated  with  a  twenty-fourth  generation, 
diluted  with  one  trillion  times  its  quantity  of  pure  water. 

Darwin  believed  that  septicaemia  could  be  produced  in  a  more 
and  more  virulent  form  with  every  successive  inoculation  from 
animal  to  animal  by  the  intensity  of  the  virus  being  increased  by 

8 


SEPTICAEMIA. 

passing  through  different  media.  Buchner  even  went  so  far  as  to 
claim  that  perfectly  harmless  bacteria  might  thus  be  made  to 
assume  pathogenic  qualities.  Koch  and  his  pupils  took  a  most 
decided  stand  against  such  mutability  of  form,  or  action  of  any 
bacteria. 

Coze  and  Feltz  (Hecherches  exp£rimentales  sur  la  presence  des 
infusoires  dans  les  maladies  infectieuses,  Strassburg,  1866)  produced 
sepsis  in  animals  by  injecting  putrid  substances  directly  into  the  cir- 
culation, and  could  not  only  demonstrate  the  presence  of  bacteria 
in  the  blood,  but  were  able  to  propagate  the  disease  from  one  ani- 
mal to  another. 

Gaft'ky  (u  Experimentell  erzeugte  Septicsemie,"  etc ,  Mitfheilun- 
gen  aus  dem  Kaiscrl.  Gesundheitsamte,  B.  i.  S.  80)  investigated 
Davaine's  septicaemia  experimentally.  He  procured  the  infection 
by  using  water  from  a  stagnant  river,  and,  by  continually  control- 
ling the  experiments  with  the  microscope,  using  Koch's  methods, 
and  working  only  with  pure  cultures,  he  was  able  to  prove  beyond 
a  doubt  that  the  theories  of  progressive  virulence  of  bacteria  were 
untenable.  He  showed  that  the  highest  degree  of  virulence  was 
already  attained  in  the  second  generation.  He  also  proved  that  the 
wrong  conclusions  were  due  to  im purification  in  the  experiments, 
and  that  when  the  proper  precautions  are  taken  in  the  process  of 
sterilization  to  prevent  the  admixture  of  other  microorganisms, 
the  introduction  of  one  kind  always  produces  in  the  same  animal 
the  same  definite  specific  result.  The  most  interesting  conclusions 
to  be  drawn  from  the  experiments  in  Koch's  laboratory,  point  to 
the  fact  that  septicaemia  is  only  a  general  term  which  includes  a 
number  of  morbid  processes,  and  this  is  well  illustrated  by  the 
injection  into  the  tissues  of  the  u  vibriones  septiques"  of  Pasteur. 
Surface  inoculation  with  these  bacilli  produced  no  effect,  their 
pathogenic  influence  became  only  evident  after  injections  into  the 
subcutaneous  connective  tissue.  Gaffky  found  that  this  bacillus 
grows  most  readily  upon  potato.  Koch  applied  to  the  condition 
produced  by  this  bacillus  the  term  u  malignant  oedema."  A  minute 
quantity  of  these  bacilli,  taken  from  a  second  potato — that  is,  a 
second  generation — injected  under  the  skin  of  a  guinea-pig  proved 
fatal  on  the  second  day  with  all  the  usual  signs  of  malignant 
oedema  and  septic  intoxication.  This  bacillus  is  not  only  contained 
in  stagnant  water,  but  can  also  be  obtained  from  garden  earth. 

Sternberg  ("  Induced  Septicaemia  in  the  Rabbit,"  American 
Journal  of  the  Medical  Sciences,  July,  1882)  produced  marked 
septicaemia  in  rabbits  by  injecting  subcutaneously  his  own  saliva 
in  small  doses.  Injections  of  1.25  to  1.75  c.c.  with  few  excep- 
tions produced  death,  usually  within  forty-eight  hours.  The  con- 
stant and  characteristic  lesion  found  was  a  diffuse  cellulitis,  or 


AKTIFICIAL    SEPTICAEMIA    IN    ANIMALS.  115 

inflammatory  oedema,  extending  in  all  directions  from  the  point 
of  injection,  attendant  with  an  abundant  exudation  of  bloody 
serum  swarming  with  micrococci.  Hemorrhagic  extravasations  in 
the  connective  tissue  and  in  various  organs  were  of  frequent  occur- 
rence, and  changes  in  the  liver  and  spleen  such  as  are  common  to 
quickly  fatal  septic  diseases,  were  commonly  found.  The  disease 
could  be  communicated  by  dipping  a  hypodermic  needle  in  the 
blood  of  a  rabbit  just  dead  as  the  result  of  an  injection  of  saliva 
and  inoculating  a  healthy  rabbit ;  a  rapidly-fatal  septicaemia  was 
produced.  Ogston  states  that  in  cases  of  septicaemia  in  man,  micro- 
cocci  are  present  in  the  blood  and  are  excreted  in  a  living  state 
in  the  urine.  This  statement  has  been  confirmed  by  Eiselsberg, 
who  examined  the  blood  of  almost  all  cases  in  Billroth's  clinic 
which  were  suffering  from  septic  fever,  and  was  able  to  demon- 
strate the  presence  of  staphylococci  and  streptococci,  most  fre- 
quently of  staphylococcus  pyogenes  albus,  in  the  blood,  and  yet 
apparently  no  abscesses  formed. 

Smith  (Annals  of  Gynecology ,  vol.  ii.  No.  12)  isolated  and  culti- 
vated from  two  cases  of  puerperal  sepsis  a  streptococcus  which  by 
inoculation  and  cultivation  experiments  differed  from  the  strepto- 
coccus of  Fehleisen  and  the  ordinary  streptococcus  of  suppuration. 
He  made  a  series  of  gelatin  cultures  with  blood  taken  from  the 
heart.  After  an  interval  of  two  or  three  days  many  colonies 
appeared.  Eats  inoculated  with  a  pure  culture  died  in  three  or 
four  days,  the  microbe  being  found  in  their  blood.  Inoculations 
were  also  made  in  the  ears  of  rabbits,  and  at  the  end  of  twenty-four 
hours  a  circumscribed  redness  without  tendency  to  diffusion  was 
apparent,  the  redness  disappearing  in  two  or  three  days.  Another 
series  of  cultures  and  inoculations  was  made  with  blood  taken 
from  the  finger  of  a  woman  sick  with  puerperal  fever,  and  this 
produced  similar  results. 

Dowdeswell  ("  Report  on  Experimental  Investigations  on  the 
Intimate  Nature -of  the  Contagion  in  certain  Acute  Infective 
Diseases,'7  British  Medical  Journal,  July  19,  1884)  has  made 
numerous  experiments  to  determine  the  nature  of  Davaine's  sep- 
ticaemia of  rabbits  and  Pasteur's  septicaemia  of  guinea-pigs. 
The  former  were  made  by  injecting  subcutaneously  five  drops  of 
putrid  ox-blood.  If  infection  was  produced,  -which  was  generally 
the  case,  death  followed  within  forty  hours  ;  characteristic  textural 
changes  in  organs  were  not  found.  One  drop  of  blood  from 
infected  animals  caused  the  death  of  a  second  animal.  Blood  from 
the  secqud  animal,  diluted  from  10  to  100,000  times,  produced  a 
fatal  effect  in  from  twenty- four  to  twenty-seven  hours.  Blood  from 
the  sixth  generation  was  diluted  ten  million  times,  and  still  produced 
a  fatal  sepsis  on  being  injected  subcutaueously ;  while  a  drop 


116  SEPTICAEMIA. 

diluted  one  hundred  million  times  produced  septicaemia  in  some 
animals  and  a  localized  suppuration  in  others.  The  microbe  ap- 
peared in  the  blood  as  small  rods  usually  arranged  in  pairs. 
Pasteur's  septicaemia  of  guinea-pigs  was  induced  by  injecting  into 
the  peritoneal  cavity  a  few  drops  of  putrid  blood  pure,  or  mixed 
with  diluted  ammonia.  Serum,  present  in  the  abdominal  cavities 
of  animals  which  had  died  of  this  disease,  in  quantities  of  0.005  to 
0.022  c.c.  injected  into  the  peritoneal  cavity  of  a  second  animal 
produced  death  from  sepsis,  while  one-tenth  of  the  quantity  re- 
quired to  induce  fatal  sepsis  proved  harmless.  The  virulence  of 
this  form  of  septicaemia  is,  therefore,  less  than  that  of  Davaine's 
rabbit  septicaemia.  The  bacillus  which  was  found  in  the  serous 
fluid  resembled  the  bacillus  of  malignant  oedema  described  by  Koch. 
The  bacillus  when  cultivated  upon  a  solid  nutrient  medium  pro- 
duced spores.  In  all  of  the  experiments  on  animals  with  septic 
microorganisms,  a  certain  interval  of  time  elapsed  between  the 
inoculation  and  the  first  appearance  of  symptoms  indicating  the 
presence  of  septicaemia.  Another  constant  feature  of  artificial 
septicaemia,  produced  by  the  introduction  of  septic  blood,  products 
of  the  septic  process,  or  cultivations  from  either  of  these,  is  that  the 
symptoms  became  more  intense  as  the  disease  progressed  ;  both  of 
these  facts  are  positive  proofs  that  the  active  agents  which  caused 
the  septicaemia  are  reproduced  in  the  body,  and  that  the  beginning 
of  the  disease  takes  place  as  soon  as  a  certain  amount  of  virus  has 
been  formed  in  the  body,  and  the  intensity  of  the  symptoms  is  pro- 
portionate to  the  quantity  of  infective  material  circulating  in  the 
blood — in  other  words,  septicaemia  caused  by  the  introduction  into 
the  organism  of  living  septic  germs  is  noted  for  its  progressive 
character,  resembling,  in  this  respect,  perfect  true  septicaemia  as  we 
observe  it  at  the  bedside  ;  differing  thus  entirely  from  another 
clinical  form  of  septicaemia  which  is  caused  by  the  introduction 
into  the  circnlation  of  preformed  toxic  substances,  and  which  has 
been  designated  by  Mathews  Duncan  as  sapraemia.  This  form  of 
septicaemia  I  will  illustrate  by  reference  to  the  experiments  which 
have  been  made  for  the  purpose  of  studying 

Septic  Intoxication  in  Animals  by  the  Introduction  of  Putrid 
Substances. 

That  putrid  substances  injected  directly  into  the  circulation  pro- 
duce symptoms  of  septic  intoxication  has  been  known  for  a  long 
time,  and  the  extensive  researches  of  Pauum  threw  additional  light 
on  this  subject.  It  was  believed  that  putrid  material  Avhen  intro- 
duced into  the  organism  induced  a  process  of  fermentation  to  which 
were  attributed  the  most  constant  post-mortem  appearances  found 


SEPTIC    INTOXICATION    IN    ANIMALS.  117 

in  septicaemic  subjects — fluidity  of  the  blood  and  softening  of  the 
tissues.  That  these  changes  were  not  necessarily  caused  by  the 
action  of  living  microorganisms  was  determined  by  experiments, 
as  the  introduction  of  putrid  blood,  or  meat  infusion  that  had  been 
boiled  for  a  considerable  length  of  time,  produced  toxic  symptoms, 
and  when  a  sufficient  quantity  was  used,  death  and  identical  patho- 
logical changes  in  the  blood  and  tissues  as  in  cases  of  true  sepsis. 
A  step  in  advance  in  the  study  of  the  action  of  putrid  substances 
was  made  by  the  discovery  of  the  ptomaines  in  an  exhumed  body 
by  Selmi  in  1872.  The  ptomaines  isolated  by  Selmi  were  volatile 
alkaloids  which  were  separated  from  a  body  some  time  after  death. 
Gautier,  independently  of  Selmi,  and  about  the  same  time,  made 
the  same  observations,  but  believed  that  the  toxic  substances  were 
volatile,  and  that  in  their  action  they  resembled  the  narcotics  mor- 
phine and  atropine,  and  were  more  closely  allied  to  the  alkaloid 
extracted  from  poisonous  mushrooms. 

Semmer  ("  Putride  Intoxication  und  septische  Infection,  Metas- 
tatische  Abscesse  und  Pysemie,"  Virchow's  Archiv,  B.  Ixxxiii.) 
gives  an  account  of  the  action  of  septic  substances  as  studied  expe- 
rimentally by  Guttmann  in  the  pathological  department  of  the 
Veterinary  School  at  Dorpat.  The  experiments  were  made  with 
putrid  substances,  products  of  inflammation,  septic  blood,  and 
cultivations  of  septic  bacteria.  These  researches  showed  that  a 
chemical,  putrid  poison  is  formed  in  putrefying  substances,  and  that 
a  certain  quantity  of  such  poison  produces  symptoms  of  sepsis  and 
death  in  animals.  The  blood  of  animals  killed  with  such  putrid 
poison  was  found  to  possess  no  infective  qualities,  and  the  usual 
putrefactive  bacteria  are  destroyed  in  the  blood,  and  only  appear 
again  after  the  death  of  the  animal.  It  was  claimed,  even  at  this 
time,  that  the  bacteria  elaborate  the  poison,  as  experiments  made 
with  cultivations  grown  outside  the  body  produced  the  same  effects. 
Another  conclusion  arrived  at  was  that  putrid  substances  adminis- 
tered subcutaueously  may  produce  gangrene,  phlegmonous  inflam- 
mation, or  erysipelas,  according  to  the  stage  of  the  putrefaction, 
temperature,  culture-soil,  etc.  The  infective  material  was  never 
found  in  the  blood,  but  always  in  the  products  of  the  inflammation. 
A  sharp  distinction  was  made  between  contagious  septicaemia  and 
putrid  intoxication.  It  was  clearly  stated  that  true  septicaemia  is 
always  preceded  by  a  stage  of  incubation,  and  that  its  contagium  is 
destroyed  by  boiling,  putrefaction,  and  germicides. 

Bergmann  (Das  putride  Gift,  etc.,  Dorpat,  1866)  isolated  from 
putrid  blood  a  crystallizable  chemical  substance  which  he  called 
sepsin,  which  when  injected  into  animals  produced  a  complexus  of 
symptoms  resembling  true  sepsis,  with  this  important  difference, 
however,  that  as  soon  as  the  toxic  substance  reached  the  circulation 


118  SEPTICAEMIA. 

the  maximum  symptoms  were  observed,  and  if  the  animal  recovered 
from  the  immediate  effects  of  the  intoxication,  it  recovered  showing 
that  the  disease  induced  resulted  from  the  introduction  of  a  pre- 
formed poison,  and  on  this  account  was  not  progressive.  Later, 
Hiller  ("  Die  Lehre  von  der  Fiiulniss,"  Centralblatt  f.  Chirurgie, 
1876)  produced  a  similar  affection  with  ferments.  Bergmann  and 
Angerer  (Das  Verhaltniss  der  Ferment-Intoxication  zur  Septicwmie, 
Festschrift  zur  Feier  des  300  jahrigen  Bestehens  der  Jul.  Maximilian 
Universitdt.  Wurzburg,  1882)  produced  a  condition  in  animals 
resembling  septicaemia  by  injecting  into  the  circulation  pepsin  and 
paucreatiu.  When  death  occurred  after  iutravascular  injections  of 
these  ferments,  fibrinous  deposits  were  found  in  the  heart  and  pul- 
monary vessels :  these  experiments  were,  therefore,  confirmatory  of 
the  observations  previously  made  by  Edelberg  and  Birck,  who  had 
shown  that  the  injection  of  putrid  substances  into  the  circulation 
materially  increased  the  free  fibrin  ferment  in  the  circulating  blood. 

Blumberg  (Virchow's  Archiv,  B.  c.  Heft  3)  concluded  from  his 
numerous  experiments  on  animals  that  the  symptoms  which  follow 
an  injection  of  putresceut  material  into  the  circulation  are  not  always 
constant ;  that,  in  fact,  extreme  prostration,  high  temperature,  rapid 
pulse  and  respiration,  are  the  only  constant  symptoms  found.  The 
same  author  also  confirmed  the  statement  that  the  blood  of  patients 
dying  from  putrid  intoxication  contained  no  microorganisms. 

Samuel  (Archivf.  Exp.  Pathologic  u.  Pharmacie,  i.  317)  believes 
that  putrid  fluids  from  the  second  day  until  the  eighth  mouth  act 
differently,  and  divides  their  action,  according  to  this  supposition, 
into  three  stages  :  1,  phlogogeuic,  in  which  they  produce  only 
inflammation ;  2,  septogenic,  in  which  they  produce  in  the  living 
organism  putrefactive  processes ;  3,  pyogenic,  in  which  they  cause 
only  suppuration,  having  lost  in  the  meantime  their  other  qualities. 

Mikulicz  ("Ueber'die  Beziehuugeu  des  glycernis  zu  Cocco-bac- 
teria  septica  u.  zur  septischeu  Infection/'  Archivf.  klin.  Chirurgie, 
B.  xxii.)  found  that  putrid  fluids,  according  as  they  are  free  from 
bacteria,  or  contain  more  or  less  of  putrefactive  germs,  will  produce 
a  slight  inflammation,  a  suppurative  inflammation,  or  a  progressive 
phlegmonous  inflammation . 

Bergmaun  (Verh.  der  Deutschen  Gesellschaft fur  Chirurgie,  1882) 
advances  the  idea  that  in  cases  of  septicaemia  the  microorganisms 
enter  the  colorless  blood-corpuscles  and  by  multiplication  cause 
their  dissolution,  during  which  the  fibrin-generators  are  liberated, 
the  process  ending  in  intravascular  coagulation  and  capillary  embo- 
lism. In  Koch's  mice-septicaemia  such  a  chain  of  pathological 
conditions  can  be  readily  demonstrated,  but  in  many  cases  of  fatal 
sepsis  in  man  the  microorganisms  in  the  blood  are  few,  no  destruc- 
tion of  leucocytes  can  be  demonstrated,  extravasations  and  capillary 


SEPTIC    INTOXICATION    IN    ANIMALS.  119 

embolism  are  absent,  hence  death  cannot  be  attributed  to  fibrin 
intoxication.  In  such  instances  we  can  only  assume  the  presence  of 
a  soluble  ptomaine,  which  is  diffused  throughout  the  entire  body 
and  destroys  life  by  its  toxic  properties. 

Frankel  ("  Ueber  Microorgauismen  der  chir.  Infections-Krank- 
heiten,"  Wiener  med.  Wochensohrift,  1885,  B.  xxxv.)  found  but  few 
micrococci  in  the  blood  of  septiceemic  patients,  and  observed  that 
they  greatly  increased  after  death  ;  but  after  the  lapse  of  some  fur- 
ther time,  altogether  disappeared,  thus  also  confirming  a  fact  pre- 
viously known,  that  putrefaction  destroyed  septic  germs.  These 
observations  may  tend  to  harmonize  the  discrepancy  of  opinion 
growing  out  of  the  different  results  obtained  by  different  experi- 
menters by  injection  of  putrid  substances,  as  some  of  the  fluids 
may  have  contained  an  abundance  of  living  microorganisms,  while 
others  may  have  been  rendered  sterile  by  age,  owing  to  advanced 
putrefaction. 

Brieger  ("  Giftige  Producte  der  Faulniss-bacterien,"  Berliner 
klin.  Wochenschrift,  1884,  No.  14)  and  Maas  ("  Faulniss-alcaloide," 
Fortschritte  der  Medicin,  1883)  have  rendered  valuable  service  in 
the  chemical  isolation  of  ptomaines  from  putrid  substances,  and  the 
results  of  their  inoculation  experiments  established  more  firmly  the 
fact  of  putrid  intoxication  by  ptomaines.  The  number  of  bacteria 
in  rabbits  killed  by  septic  infection  is  so  great,  that  death  may 
ensue  from  simple  mechanical  causes,  while,  in  fatal  cases  of  sepsis 
in  man,  the  number  is  often  so  small  that  it  seems  natural  to 
suppose  that  the  microorganisms  are  capable  of  producing  some 
poisonous  substance  which  destroys  the  patient  before  they  have 
time  to  multiply  to  the  extent  observed  in  the  septicaemia  of  rabbits 
and  mice. 

Hauser  (Ueber  Faulniss-bacterien  und  der  en  Beziehung  zur  Septi- 
ccemie,  Leipzig,  1885)  succeeded  in  isolating  three  kinds  of  schizo- 
mycetes  from  a  putrid  meat  solution,  which  he  called,  respectively, 
proteus  vulgaris,  mirabilis,  and  Zenkeri.  He  claimed  that  all  of 
them  changed  their  form  during  their  growth,  appearing  at  differ- 
ent times  as  cocci,  long  and  short  rods,  vibriones,  spirilli,  etc.  (Fig. 
5.)  The  variety  in  form,  he  claims,  was  influenced  by  the  nature 
of  the  culture  substance.  All  these  bacteria  are  putrefactive  agents 
and  the  proteus  vulgaris  and  mirabilis  are  most  frequently  present. 
The  experiments  were  made  by  removing  organs,  or  part  of  organs, 
from  animals  immediately  after  death,  and  placing  them  in  steril- 
ized vessels,  where  they  were  inoculated  with  pure  cultivations  of 
the  proteus.  A  sterilized  emulsion  of  boiled  meat  and  eggs,  inocu- 
lated with  a  culture  of  the  three  kinds  of  proteus,  was  transformed 
into  a  putrescent  mass  in  a  short  time.  That  this  change  was  not 
caused  by  a  preformed  putrefactive  ferment  was  proved  by  the  fact 


120 


SEPTICAEMIA. 


that  when  the  decomposed  mass  was  filtered  through  clay  cells  the 
filtrate  did  not  produce  the  same  effect.  A  small  amount  of  the 
putrescent  fluid  injected  into  the  tissues  of  animals  produced  intense 
symptoms  of  intoxication  and  sometimes  death  within  an  hour. 


FIG.  5. 


Proteus  vulgaris,  285  :  1. 


Injections  into  the  subcutaneous  tissue  of  rabbits  of  a  pure  culture 
of  the  proteus  vulgaris  and  mirabilis  not  infrequently  caused  exten- 
sive abscesses.  An  alcoholic  extract  of  the  putrid  meat  proved  less 
toxic,  but  a  large  quantity  also  produced  sepsis  and  death. 

Rosenberger  ("Experimeutell  Studieniiber  Septicsemie,"  Central- 
blattf.  d.  med.  Wiss.,  1882,  No.  4)  studied  experimentally  on  rabbits 
the  effect  of  injections  of  putrid  blood.  In  one  series  of  experi- 
ments he  simply  injected  the  putrid  material,  in  another  he  boiled 
the  fluid  before  injecting  it.  The  result  was  the  same  —  typical 
septicaemia,  only  that  the  animals  infected  with  the  boiled  material 
required  a  larger  dose  and  did  not  succumb  so  rapidly  to  the  sepsis. 
Microscopical  examination  of  the  blood  and  culture  experiments 
yielded  the  same  results  :  the  presence  of  bacteria  and  their  growth 
upon  culture  media.  He  is  of  the  opinion  that  in  septicaemia 
bacteria  are  not  the  first  or  the  essential  etiological  condition,  but 
believes  that  under  certain  circumstances  innocent  bacteria  which 
may  exist  in  the  body  are  transformed  within  twenty-four  to  forty- 
eight  hours  into  specific  septic  bacteria.  In  his  experiments  he 
attributed  the  occurrence  of  sepsis  to  the  introduction  of  the  septic 
poison,  boiled  or  unboiled.  The  most  interesting  proof  that  true 
progressive  sepsis  is  not  the  result  of  the  introduction  into  the  cir- 
culation of  the  products  of  putrefaction,  but  of  pathogenic  germs, 


SEPTIC    INTOXICATION    IN    ANIMALS.  121 

has  been  furnished  by  Tiegel  (Dissertation,  Bern,  1871).  By  in- 
jecting putrid  fluids  into  animals  he  produced  true  progressive  sep- 
ticaemia. He  then  resorted  to  filtration  of  the  fluid  through  clay 
cells,  so  as  to  separate  from  it  any  organic  germs  it  might  contain, 
and  showed  that  fluid,  thus  treated,  was  rendered  perfectly  sterile, 
and  that,  when  injected,  it  produced  only  putrid  intoxication  and 
no  progressive  sepsis. 

Binne  ("Der  Eiterungs  process  uud  seine  Metastasen,"  Archivf. 
klin.  Chirurgie,  B.  xxxix.  S.  21)  asserts  that  the  chemical  product 
of  pus-microbes  alone,  as  well  as  sterilized  putrid  fluids,  never  pro- 
duces metastases.  He  sterilized  fluid  cultures  of  the  staphylococcus 
pyogenes  aureus  after  filtration,  and  injected  directly  into  the  blood- 
vessels of  rabbits  as  much  as  four  grammes  of  this  fluid,  and  in 
dogs  increased  the  dose  to  fourteen  grammes.  Many  of  the  animals 
showed  slight  symptoms  of  toxasmia,  somnolence,  diarrhoea,  and 
collapse.  By  using  still  larger  doses  the  symptoms  were  intensified 
and  the  animals  died.  Metastatic  abscesses  were  never  found. 

Hoffa  (  Verh.  der  Deutschen  Gesettschaft  f.  Chirurgie,  1889)  has  re- 
cently made  some  very  interesting  observations  on  the  immediate  cause 
of  death  in  rabbits  inoculated  with  a  pure  culture  of  Koch-Gaff  ky's 
bacillus.  The  animals  were  inoculated  at  the  base  of  the  ear,  and 
immediately  after  death  the  ptomaines  were  isolated  by  Brieger's 
method.  In  every  instance  he  obtained  a  substance  called  methyl- 
guanidin, which  on  chemical  analysis  was  shown  to  consist, of  the 
formula  C2H7N3.  When  this  substance  was  injected  into  rabbits 
it  produced  symptoms  of  intoxication  which  resembled  in  every 
respect  those  produced  by  the  injection  of  the  pure  cultures 
obtained  from  septicaemic  rabbits.  As  methylguanidin  could  not 
be  produced  from  the  cadavers  of  healthy  animals  by  the  same 
method,  Hoffa  naturally  came  to  the  conclusion  that  it  was  a  product 
of  the  bacteria,  and  that  death  was  to  be  attributed  to  the  produc- 
tion of  this  substance  in  the  tissues  of  the  infected  animals.  The 
source  of  methylguanidin  in  the  body  is  kreatin,  and  the  bacteria 
must  possess  the  property  of  oxidation,  as  kreatin  is  transformed 
into  methylguanidin  only  by  oxidation. 

Septicaemia  in  man  corresponds  with  the  two  forms  produced, 
experimentally,  in  animals  :  1.  True  progressive  septicaemia,  caused 
by  the  introduction  of  microbes  into  the  tissues,  where  they  mul- 
tiply and  later  reach  the  blood  ;  where  mural  implantation  and 
capillary  embolism  and  thrombosis  take  place,  which  directly  inter- 
fere with  the  proper  nutrition  and  function  of  important  organs, 
and  where  the  septic  intoxication  is  caused  by  the  formation  of 
ptomaines  in  the  organism.  For  this  form  of  sepsis  Neelsen  (Ver- 
handl.  der  Deutschen  Gesettschaft  f.  Chirurgie,  1884),  has  suggested 
the  name  acute  mycosis  of  the  blood,  to  distinguish  it  from  the 


122  SEPTICAEMIA. 

second  form — 2.  Saprsemia,  putrid  intoxication,  or,  as  Neelsen 
terras  it,  toxic  mycosis  of  the  blood,  in  which  few  or  DO  microbes  are 
found  in  the  blood,  and  in  which  death  is  due  entirely  to  the  pres- 
ence of  ptomaines.  In  the  first  variety  it  seems  that  the  infection 
is  generally  due  to  the  presence  of  pus-microbes  which  either  reach 
the  circulation  directly  by  permeating  the  vessel  wall,  or  enter 
indirectly  through  the  lymphatic  channels.  The  latter  mode  of 
infection  gives  rise  to  the  most  acute  and  fatal  form  of  septicaemia. 
Saprsemia,  or  putrid  intoxication,  represents  that  form  of  septicaemia 
in  animals  in  which  a  preformed  toxic  agent,  as  boiled  putrid  sub- 
stances or  a  toxic  alkaloid,  is  injected  into  the  circulation,  and  in 
which  the  maximum  symptoms  are  reached  as  soon  as  the  poison 
has  become  mixed  with  the  blood.  This  form  of  sepsis  may  be 
caused  by  any  microbes,  otherwise  harmless,  or  only  with  slight 
pathogenic  properties,  as  the  bacilli  of  putrefaction,  which  cause 
putrefaction  in  any  dead  tissue,  as,  for  instance,  a  blood-clot  or 
contused  tissue ;  and  the  symptoms  arise  as  the  ptomaines  are  ab- 
sorbed, and  are  proportionate  to  the  amount  absorbed,  and  subside 
with  the  cessation  of  absorption  and  their  elimination  through  some 
of  the  excretory  organs. 

Septico-pycemia. 

Septico-pysemia  is  a  condition  in  which  the  symptoms  indicate 
the  presence  of  both  septicaemia  and  pyaemia,  and  in  which  the 
post-mortem  appearances  point  to  septic  and  purulent  infection. 
Leube  ("  Zur  Diagnose  der  spontaneu  Septico-pysemie,"  Dcutsches 
Archivf.  Jdin.  Medicin,  B.  xxii.  S.  335)  first  described  this  affection 
and  called  it  spontaneous,  because  he  was  unable  to  trace  the  source 
of  infection  from  without  in  the  cases  which  came  under  his  obser- 
vation. Litten  ("  Ueber  septische  Erkrankungen  interner  Art, 
namentlich  hamorrhagische  Sepsis  interna,"  Zeitschrift  f.  klin.  Medi- 
cin,  B.  ii.),  on  the  other  hand,  was  always  able,  in  his  cases,  to  locate 
the  infection-atrium,  but  the  primary  infection  at  the  time  acute 
symptoms  appeared  had  either  disappeared  or  its  location  could 
only  be  ascertained  by  a  most  careful  examination.  Jiirgensen 
(Berliner  klin.  Wochenschrift,  JSTo.  18,  1888)  calls  it  '<  Krypto- 
genetic  Septico-pysemia/7  as  he  was  unable  to  find  a  tangible  infec- 
tion-atrium. He  gave  an  account  of  one  hundred  cases  which  had 
come  under  his  own  personal  observation.  The  patients  were 
usually  attacked  first  with  an  angina,  and,  as  this  stage  was  gener- 
ally attended  by  a  chill  and  a  general  feeling  of  malaise,  the 
patients  usually  attributed  it  to  a  cold.  In  most  cases  the  general 
infection  was  announced  by  a  severe  chill.  Rapid  loss  of  strength 
was  one  of  the  most  prominent  symptoms,  so  that  in  a  very  few 


SEPTICO-PY^MIA.  123 

days  the  patients  became  utterly  prostrated.  The  symptoms  which 
pointed  to  local  processes  during  life  were  referred  most  frequently 
to  the  lungs,  liver,  spleen,  pleura,  heart,  and  the  long  bones. 
Whether  the  primary  infection  occurred  through  the  pharynx, 
where  the  first  symptoms  were  manifested,  could  not  be  definitely 
ascertained.  In  the  acute  cases,  the  symptoms  were  grave  from 
the  beginning  and  increased  as  the  infection  progressed,  while  in 
chronic  cases,  infection  is  maintained  from  some  suppurating  focus, 
and  the  disease  may  become  prolonged  for  several  years.  Subcuta- 
neous and  retinal  hemorrhagic  extravasations  were  frequently 
observed.  The  post-mortem  examinations  revealed  suppuration  in 
some  of  the  internal  organs  and  vascular  conditions  which  are 
found  in  cases  of  sepsis.  These  cases  may  be  compared  with  acute 
suppurative  osteomyelitis,  where  often  the  most  careful  inquiry 
and  the  most  scrutinizing  examination  fail  in  furnishing  reliable 
evidences  for  locating  the  primary  source  of  infection.  It  is  possi- 
ble that  the  pus-microbes  have  gained  entrance  through  an  intact 
mucous  surface,  or  through  the  skin,  and  that  they  have  remained 
in  a  latent  condition  until  a  locus  minoris  resistentice  is  created 
somewhere  in  the  body,  where  they  localize  in  a  soil  prepared  for 
their  growth  and  multiplication,  or,  what  is  more  likely  the  case, 
they  entered  through  an  abrasion  or  slight  lesion,  which  may  have 
been  so  insignificant  that  the  patient  himsejf  failed  to  notice  it,  and 
produced  no  symptoms  until,  by  accident  or  disease,  a  proper  soil 
was  prepared  for  the  initiation  of  an  acute  attack  in  one  or  more  of 
the  internal  organs. 


CHAPTEK  XI 

PYAEMIA. 

THE  presence  of  pyaemia  in  over-crowded  and  badly-ventilated 
hospitals  during  the  time  before  the  antiseptic  treatment  of  wounds 
came  into  use,  gave  rise  to  the  general  belief  that  the  disease  was 
due  to  a  specific  cause,  and  ever  since  bacteriology  became  a  science 
diligent  search  has  been  made  to  demonstrate  its  specific  microbic 
origin.  Since  the  discovery  of  the  microbes  of  suppuration,  new 
light  has  been  shed  upon  the  etiology  and  pathology  of  this  disease. 
Bacteriological  studies  of  pyaemic  products  have  shown  that  one  or 
more  kinds  of  pus-microbes  are  always  present,  thus  establishing 
the  direct  relationship  between  a  suppurating  process  in  some  part 
of  the  body,  and  the  development  of  metastatic  or  pyaemic  abscesses. 
Clinical  experience  has  only  corroborated  the  scientific  investiga- 
tions of  this  subject,  inasmuch  as  it  has  shown  that  the  frequency 
of  its  occurrence  has  been  diminished  in  proportion  to  the  lessening 
of  suppurative  inflammation  in  wounds  under  the  antiseptic  man- 
agement of  traumatic  injuries  and  internal  suppurating  lesions. 
We  are  justified  upon  the  basis  of  well-established  facts  in  claiming 
that  pyaemia  is  not  a  disease  per  se,  but  that  its  occurrence  depends 
upon  an  extension  of  a  suppurative  process  from  the  primary  seat 
of  infection,  and  suppuration  in  distant  organs  by  the  transporta- 
tion of  emboli  infected  with  pus-microbes  through  the  systemic 
circulation.  The  distant,  or  metastatic  abscesses  contain  the  same 
microbes  which  are  found  in  the  wound  secretions  or  the  abscess 
from  which  the  general  purulent  infection  took  place.  Experiments 
have  shown  that  a  culture  of  pus-microbes  from  a  furuncle  may 
produce  pyaemia  in  animals,  and  that  the  microbes  cultivated  from 
a  pyaemic  abscess  when  injected  under  the  skin  of  an  animal  cause 
only  a  localized  suppurative  inflammation  without  any  general 
symptoms. 

Artificial  Production  of  Pycemia  in  Animals. 

Koch  (Untersuchungen  ilber  die  Aetiologie  der  Wund  infections 
Krankheiten,  Leipzig,  1878)  produced  typical  pyaemia  in  rabbits 
by  injecting  a  putrid  fluid,  obtained  by  maceration  of  the  ear  of  a 
mouse,  into  the  subcutaneous  connective-tissue  in  the  inguinal 


AETIFICIAL    PEODUCTION    IN    ANIMALS.  125 

9 

region.  A  large  abscess  was  found  at  the  point  of  injection  and 
numerous  metastatic  abscesses  in  the  internal  organs.  In  the  pus 
of  these  abscesses  he  found  a  micrococcus  which  he  considered  as 
characteristic  of  this  affection. 

Klein  (Microorganisms  and  Disease,  1885)  described  a  micro- 
coccus  of  pyaemia  in  mice.  Certain  cocci  which  were  present  in 
pork-broth  proved  fatal  to  mice  in  about  a  week,  producing  puru- 
lent inflammation  at  the  point  of  injection  and  metastatic  abscesses 
in  the  lungs.  Fresh  inoculations  in  mice  again  produced  a  fatal 
result  with  pyaemic  symptoms. 

Pawlowsky  found  that,  by  the  simultaneous  injection  of  sterilized 
cinnabar,  and  of  cultivations  of  staphylococcus  pyogenes  aureus 
into  the  circulation,  he  produced  abscesses  in  various  organs — in 
fact,  the  typical  picture  of  pyaemia.  The  presence  of  particles  of 
foreign  bodies  rendered  material  aid  in  the  development  of  metas- 
tatic abscesses,  as  the  mere  arrest  of  pus-microbes  in  the  circulation 
without  them,  as  a  rule,  is  not  sufficient  of  itself  to  lead  to  the 
production  of  true  pyaemia.  In  rabbits,  even  the  introduction  of 
a  large  quantity  of  a  culture  of  pus-microbes  into  the  circulation 
does  not  produce  pyaemia.  Twenty-four  hours  after  the  injection 
the  microbes  may  be  found  in  large  numbers  in  the  pulmonary  and 
other  capillaries,  but  after  forty-eight  hours  they  have  all  disap- 
peared from  the  circulation.  If  the  cocci  are  suspended  in  an 
embolus,  this  latter,  by  producing  alterations  in  the  endothelia  of 
the  bloodvessels  in  which  it  has  become  impacted  produces  a  locus 
minoris  resistentice  favorable  to  the  growth  of  germs.  In  the  ex- 
periments of  Pawlowsky,  the  particles  of  cinnabar  acted  upon  the  en- 
dothelia lining  the  capillary  vessels  in  the  same  manner  as  the  frag- 
ments of  a  thrombus  by  impairing  the  local  nutrition  of  the  tissues 
at  the  point  of  impaction.  If  pyaemia  is  produced  in  guinea-pigs, 
or  mice,  with  infectious  pus,  or  with  a  pure  cultivation  of  the  same, 
the  same  local  conditions  are  produced  which  invariably  precede 
the  development  of  pyaemia  in  man.  Some  of  the  veins  at  the 
seat  of  primary  infection  are  invaded  by  pus-microbes  and  become 
blocked  by  a  thrombus,  this  thrombus  undergoes  puriform  soften- 
ing, small  fragments  containing  pus-microbes  become  detached, 
and  are  washed  away  and  enter  the  general  circulation  as  emboli, 
which,  when  they  become  arrested,  establish  independent  centres 
of  suppuration.  In  such  cases  the  pus-microbes  are  present  in 
the  blood,  in  the  tissues  around  the  abscess,  and  in  all  purulent 
collections. 


126  PY.EMIA 


The  Relations  of  Pas-microbes  to  Pyaemia  in  Man. 

Rosenbach  (Mwroorganismen  bei  den  Wundinfections  Krankheiten 
des  Menschen,  Wiesbaden,  1884)  examined  six  cases  of  typical 
pyaemia  with  a  view  to  determine  the  nature  of  the  microorganisms 
present  in  pyaemie  patients.  He  found  the  streptococcus  pyogenes 
present  in  the  blood  and  metastatic  deposits  in  five  of  them ;  in 
two  of  these  cases,  staphylococci  were  also  present,  although  fewer 
in  number.  In  only  one  of  them  he  found  staphylococci  alone,, 
and  this  case  recovered. 

Pawlowsky  ("  Beitrage  zur  Aetiologie  der  Pyaemie,"  Centralblatt 
f.  d.  med.  Wissen.,  1887,  JN"os.  24,  25)  made  a  bacteriological  exam- 
ination of  the  pus  of  metastatic  abscesses  in  five  cases  of  pyaemia. 
In  four  cases  he  found  staphylococcus  pyogenes  aureus,  and  in  the 
fifth  case,  which  was  remarkable  for  the  extent  of  the  joint  compli- 
cations, he  found  the  streptococcus  pyogeues.  He  believes  that  the 
staphylococcus  aureus  is  the  usual  cause  of  pyaemia,  and  especially 
of  that  form  characterized  by  multiple  abscesses  in  the  internal 
organs.  Large  cultures  of  this  coccus  suspended  in  water  and 
injected  subcutaneously  in  rabbits  caused  death,  and  at  the  necropsy 
multiple  abscesses  were  found.  He  believes  that  pyaemia  in  man 
occurs  when  disturbances  in  the  circulation  are  present,  so  that 
floating  cocci  find  places  for  localization  within  the  bloodvessels. 
He  produced  these  disturbances  artificially  by  making  intravenous 
injections  of  cinnabar,  and  ascertained  that  the  presence  of  the 
granular  material  determined  the  localization  of  the  microbes. 

Besser,  of  St.  Petersburg,  writes  in  Wratch  (St.  Louis  Medical 
Journal,  May  2,  1888,  Nos.  19  and  20)  that  he  has  examined, 
bacteriologically,  blood,  pus,  and  parenchymatous  fluid  from  organs 
in  23  cases  of  pyaemia.  In  8  cases,  the  staphylococci  albi  and 
aurei  were  found;  in  14,  the  streptococci ;  and  in  1,  the  strepto- 
cocci and  staphylococci  simultaneously.  The  microbes  were  dis- 
covered, (a)  during  the  patient's  life  in  pus  in  every  one  out  of  20 
cases  examined ;  in  blood,  in  11  of  12  :  and  in  parenchymatous 
serum,  in  1  of  1  ;  (b)  after  death,  in  pus,  in  17  of  17 ;  in  blood,  4 
of  9 ;  and  in  organs,  9  of  14.  Besser's  predecessors  described  23 
additional  cases  of  pyaemia,  in  14  of  which  staphylococci  were 
found,  in  7  streptococci.  Total,  46  cases  :  in  22  staphylococci.  in 
21  streptococci,  in  3  both.  Besser  has  also  observed  that  the 
staphylococcus  aureus  could  transform,  under  certain  conditions, 
into  staphylococcus  albus,  and  vice  versa.  He  was  unable  to  dis- 
cover the  slightest  difference  between  the  microbes  of  suppuration 
and  those  of  pyaemia. 

Schuller  ("  Ueber  Bacterien   bei  metastatischen  Gelenkentztin- 


RELATIONS    OF    PUS-MICROBES    TO    PYAEMIA.        127 

dungen,"  Verh.  der  Deutschen  O-eselhchaft  /.  Chiruryie,  J884) 
examined  the  contents  of  metastatic  joint  affections  in  twelve  cases 
of  puerperal  pyaemia  and  invariably  found  streptococci,  single  and 
diplococci,  but  never  bacilli. 

Okinschitz  (Dissertation,  St.  Petersburg.  1889)  made  the  rela- 
tionship which  exists  between  the  pus-microbes  and  pyaemia  the 
subject  of  bacteriological  investigation.  He  found  that  pysemic 
blood  invariably  contained  either  the  streptococcus  pyogenes  or 
staphylococcus  pyogenes  aureus,  demonstrable  by  cultivation  and 
ordinary  microscopical  examination.  As  the  hsemic  microbes 
seldom  show  any  signs  of  fission,  as  compared  with  the  bacteria  at 
the  primary  focus,  it  is  reasonable  to  infer  that  proliferation  takes 
place  mainly  in  the  pus  and  not  in  the  blood,  hence  the  great 
importance  of  thorough  disinfection  and  destruction  of  primary 
foci.  The  number  of  microbes  in  the  circulating  blood  bears  a 
direct  relation  to  the  gravity  of  the  disease ;  if  they  are  abundant 
even  in  the  absence  of  metastases  in  internal  organs  the  prognosis 
is  grave,  and  if  scanty  even  when  metastatic  foci  exist  the  prospects 
of  a  favorable  termination  are  better. 

The  occurrence  of  pyaemia  from  suppurating  wounds  or  abscesses 
does  not  depend  so  much  upon  the  kind  of  pus-microbes  which 
have  caused  the  suppuration  as  upon  surrounding  circutnstances. 
The  location  and  anatomical  structure  of  the  tissues  in  which  the 
primary  infection  has  taken  place  exert  an  important  influence  in 
the  production  of  the  disease.  It  is  well  known  that  suppurative 
inflammation  of  the  medullary  tissue  in  bone  is  exceedingly  prone 
to  give  rise  to  pyaemia.  Osteomyelitis,  without  direct  infection 
through  a  wound,  is  always  due  to  an  iutravascular  infection — 
localization  of  pus-microbes  in  the  capillary  vessels  of  the  medul- 
lary tissue.  The  microbes  come  first  in  contact  with  the  endothelial 
cells  after  mural  implantation  has  taken  place,  and  the  resulting 
coagulation-necrosis  in  the  tissues  of  the  wall  of  the  bloodvessels 
leads  to  thrombosis.  The  products  of  the  intravascular  coagulation- 
necrosis  furnish  a  most  favorable  nutrient  substance  for  the  growth 
and  multiplication  of  germs,  consequently  the  area  of  intravascular 
infection  is  rapidly  increased.  The  growth  of  the  thrombus  in  a 
proximal  direction  soon  leads  to  extensive  thrombo-phlebitis,  and, 
as  softening  of  the  thrombus  takes  place,  to  embolism  and  metas- 
tatic suppuration.  Pyaemia  following  a  suppurative  inflammation, 
in  a  wound,  or  in  the  course  of  a  phlegmonous  inflammation  in  the 
connective-tissue,  is  the  result  of  an  extra  vascular  infection.  The 
pus-microbes  coming  first  in  contact  with  the  outer  coats  of  the 
veins,  give  rise  to  a  phlebitis,  which  progresses  from  without 
inward,  and  which  is  followed  by  thrombosis  as  soon  as  the  iutima 
is  reached.  The  intravascular  dissemination  of  the  pus-microbes- 


128  PYAEMIA. 

then  takes  place  in  the  same  manner  as  in  cases  of  intravascular 
infection  after  thrombo-phlebitis.  Ordinary  pyogenic  microbes 
may  and  do  cause  pyaemia  if  they  enter  the  blood  attached  to  por- 
tions of  blood-clot,  or  other  solid  materials,  which  after  they  have 
become  impacted  in  bloodvessels  by  embolism,  prepare  the  soil  in 
distant  organs  for  their  localization  and  multiplication.  The 
importance  of  thrombosis  and  embolism  as  factors  in  the  causation 
of  pyaemia  has  been  clearly  established  by  clinical  observation  and 
experimental  research.  Emboli  may  originate  in  the  lymphatic 
vessels  when  these  are  the  seat  of  invasion  by  pyogenic  microbes, 
which,  however,  is  very  seldom  the  case.  In  chronic  pyaemia,  in 
which  multiple  metastatic  abscesses  are  formed,  embolism  takes  no 
essential  part  in  the  process,  the  microbes  enter  the  circulation  and 
are  brought  in  direct  contact  by  mural  implantation  with  the  tissues 
weakened  by  injury,  or  other  debilitating  causes.  Experimental 
research  has  shown  conclusively  that  the  introduction  of  pus- 
microbes  into  the  circulation  is  not  necessarily  or  even  usually 
followed  by  pyaemia,  and  their  accidental  entrance  in  the  course  of 
a  suppurative  inflammation  is  not  always  followed  by  serious  con- 
sequences. There  can  be  no  doubt  that  some  pus-microbes  reach 
the  circulation  in  nearly  every  case  of  suppuration,  but  their  patho- 
genic action  is  prevented,  or  neutralized,  by  an  adequate  resistance 
on  the  part  of  the  tissues  with  which  they  are  brought  in  contact 
and  their  rapid  elimination  through  healthy  excretory  organs.  A 
limited  number  of  pus-microbes  injected  into  the  circulation  of  a 
healthy  animal,  or  accidentally  introduced  into  the  blood  of  an  other- 
wise healthy  person,  are  effectively  disposed  of  by  the  white  blood- 
corpuscles.  If,  however,  the  same  number  of  microbes  are  present 
in  combination  with  fragments  of  a  blood-clot,  the  latter  produce 
such  alterations  in  the  tissues  surrounding  them  as  to  prepare  the 
parts  for  their  pyogenic  action.  The  same  happens  if  free  pus- 
microbes  localize  in  a  part  the  vitality  of  which  has  been  previously 
diminished  by  a  trauma,  or  antecedent  pathological  changes,  which 
constitute  a  locus  minoris  resistenfice  for  the  growth  and  reproduction 
of  pathogenic  microorganisms.  Pyaemia,  therefore,  must  be  looked 
upon  rather  as  a  serious  and  fatal  complication  of  suppurative 
lesions  rather  than  an  independent  specific  disease. 


CHAPTER    XII. 

ERYSIPELAS. 

HISTORY. — The  contagiousness  of  erysipelas  has  been  recognized 
for  centuries,  and  on  this  account  early  attempts  were  made  to 
include  it  among  microbic  diseases. 

jSTepveau  (Virchow  u.  Hirsch's  Jahresbericht,  1872,  1,  p.  254) 
found  micrococci  in  the  blood  of  erysipelatous  patients,  and  these 
were  present  in  greatest  number  in  blood  taken  from  the  diseased 
part. 

Wilde  (Med.  Jahrb.,  B.  civ.,  Heft  1,  S.  104)  from  his  own  inves- 
tigations was  able  to  corroborate  these  observations,  but  he  also 
ascertained  that  the  pus  of  wounds  from  which  erysipelatous 
inflammation  starts  contains  the  same  micrococci. 

Orth  (Archiv  f.  Exp.  Pathol  u.  PharmakoL,  B.  i.  S.  81)  found 
micrococci  in  the  contents  of  the  bullae  of  erysipelas.  Reckling- 
hausen  and  Lukomsky  (Virchow's  Archiv,  B.  Ix.  S.  418)  found 
micrococci  in  the  lymphatic  vessels  and  the  connective-tissue  spaces 
in  the  structures  affected  by  the  virus  of  erysipelas. 

Billroth  and  Ehrlich  (Langenbeck's  Archiv,  B.  xx.  S.  418)  found 
micrococci  not  only  in  the  lymphatic  vessels,  but  also  in  the  blood- 
vessels of  the  inflamed  skin. 

Tillmanns  (Deutsche,  med.  Wochenschrift,  1878,  No.  17)  found 
them  in  the  skin,  and  Letzerich  (Virchow  u.  Hirsch's  Jahresb., 
1875,  p.  69)  in  cases  of  erysipelas  attacking  vaccination-wounds, 
in  the  wound  itself,  in  the  bloodvessels,  muscles,  liver,  spleen,  and 
kidneys.  Koch  (Investigations  into  the  .Etiology  of  Traumatic  Infec- 
tive Diseases,  London,  1880)  described  the  specific  organism  of 
erysipelas  as  a  small  micrococcus  of  globular  shape,  united  in  pairs 
or  forming  short  chains,  and  published  photographic  representa- 
tions of  them  in  his  work,  in  which  he  also  describes  erysipelas  in 
rabbits  which  he  produced  artificially  by  the  injection,  into  the 
subcutaneous  tissue  of  the  ear,  of  mouse's  dung  softened  in  distilled 
water. 

Fehleisen  (Die  Aetiologie  des  Erysipels,  Berlin,  1883)  was  the 
first  who,  in  1883,  discovered  the  essential  cause  of  erysipelas  and 
succeeded  in  cultivating  the  microbes  on  a  number  of  nutrient 
media.  From  the  appearance  of  the  microbe  and  its  direct  etio- 
logical  bearings  to  erysipelas,  he  called  it  the  streptococcus  of  ery- 

9 


130  ERYSIPELAS. 

sipelas.  With  a  pure  culture  of  this  germ  he  produced  by  inocu- 
lation, not  only  only  erysipelas  in  animals  to  prove  its  specific 
pathogenic  qualities,  but  inoculations  were  also  made  in  man  for 
therapeutic  purposes. 

DESCRIPTION  OF  THE  STREPTOCOCCUS  ERYSIPELATOSUS. — 
Minute  cocci,  three  to  four  micro-millimetres  in  diameter,  arranged 
in  chains,  found  in  erysipelatous  skin  and  in  the  fluid  of  erysipe- 
latous bullse.  They  occupy  the  lymphatic  channels  of  the  skin 
and  spread  along  them  as  the  disease  advances.  Each  coccus 
when  it  is  about  to  divide  becomes  larger  and  oval,  and  soon 
appears  made  up  of  two  hemispherical  masses,  the  two  new  cocci 
resulting  from  fission  of  the  old  one.  Morphologically,  the  strep- 
tococcus of  erysipelas  and  the  streptococcus  pyogenes  are  nearly 
identical,  only  that  the  coccus  of  erysipelas  is  somewhat  larger,  and 
both  are  somewhat  smaller  than  the  staphylococci. 

CULTIVATION  EXPERIMENTS. — The  streptococcus  of  erysipelas 
can  be  cultivated  upon  gelatin  or  agar-agar.  The  appearances  of 
cultures  resemble  very  strongly  those  of  streptococcus  pyogenes. 
There  is  less  tendency,  however,  to  the  formation  of  terraces,  the 
margin  is  thicker  and  more  irregular  in  outline,  and  the  appear- 
ance of  the  growth  is  more  opaque  and  whiter.  Rosenbach  men- 
tions as  another  distinguishing  feature  between  the  two,  that  the 
culture  of  the  coccus  of  erysipelas  represents  upon  solid  nutrient 
media  the  shape  of  a  fern,  while  the  outlines  of  the  cultures  of  the 
pus  streptococcus  describe  the  shape  of  an  acacia  leaf. 

The  culture  appears  as  a  very  delicate  grayish-white  film.  The 
growth  is  very  slow,  and  the  individual  colonies  remain  small. 
They  do  not  liquefy  gelatin. 

INOCULATION  EXPERIMENTS. — The  characteristic  erysipelatous 
blush  is  produced  by  inoculating  these  microorganisms  into  the  ear 
of  a  rabbit. 

Krause  obtained  positive  results  by  inoculating  gray  mice. 
The  animals  died  after  three  or  four  days,  even  when  only  a  minute 
quantity  of  the  culture  was  injected  under  the  skin  of  the  back. 
Passet  inoculated  white  mice  that  had  been  liberally  fed  on  bread, 
milk,  and  oats,  and  obtained  only  negative  results.  Of  seven 
persons  inoculated  by  Fehleisen  (u  Ueber  die  Zuchtung  der  Ery- 
sipelcoccen  auf  kiinstlichen  Niihrbodeu  und  ihre  Uebertragbarkeit 
auf  Menschen."  Sitzungsbericht  der  Wurzburger  Physic,  med. 
G-eselhcha/t,  1882)  the  subjects  of  incurable  tumors,  with  pure 
cultures,  six  developed  typical  erysipelas ;  in  the  seventh  case,  the 
patient  had  suffered  from  an  attack  of  erysipelas  only  a  few  weeks 
previously,  and  was,  in  all  probability,  still  protected  against  a 
new  attack.  This  patient  was  inoculated  a  second  time  with  a 
negative  result.  Several  times  a  second  inoculation  failed  after  a 


PLATE    IV. 


«.«,» 


Chain  cocci.     962  diam. 

a.  From  erysipelas.     (Fehleisen.) 

b.  From  Phlegmon.     (After  Rosenbach  ) 


INOCULATION    FOE    THERAPEUTICAL    PUEPOSES.       131 

successful  inoculation.  The  period  of  incubation  was  fixed  at 
from  fifteen  to  sixty-one  hours.  The  microbe  was  only  found  in 
the  lymphatic  vessels  and  connective-tissue  spaces,  and  when  the 
culture  was  pure  never  produced  suppuration. 

Whitney  ("  Notes  on  Blood-changes  in  Erysipelas,"  Philadelphia 
Medical  Times,  1883)  claims  that  he  found  the  streptococcus 
erysipelatosus  in  the  blood  in  five  out  of  six  cases  of  erysipelas. 
Most  all  authorities  who  have  studied  the  subject  with  the  greatest 
care  assert,  however,  that  it  is  only  found  in  the  lymphatic  vessels 
and  never  in  the  bloodvessels. 

INOCULATION  FOR  THERAPEUTIC  PURPOSES. — Fehleisen  has 
seen  by  this  treatment  a  cancer  of  the  breast  become  smaller,  a 
lupus  disappear  almost  completely,  while  a  case  of  fibro-sarcoma 
and  another  of  sarcoma  were  not  materially  affected  by  this  method 
of  treatment. 

Kleeblatt  (Munch,  med.  Wochenschrift,  March,  1890)  reports  the 
case  of  a  lympho-sarcoma  followed  by  infection  of  the  cervical 
glands,  in  which  the  tumors  diminished  markedly  in  size  under 
the  influence  of  an  intercurrent  attack  of  erysipelas,  but  continued 
to  develop  after  this  had  passed  off.  The  patient  was  afterward 
intentionally  inoculated  with  a  pure  culture  of  the  streptococcus  of 
erysipelas,  but  the  effect  was,  as  before,  only  a  temporary  one,  as  the 
tumors  steadily  increased  in  size,  the  patient  dying  of  exhaustion. 
In  another  case  of  lympho-sarcoma  of  the  neck,  erysipelas  was 
inoculated  with  good  results,  as  the  tumor  was  found  to  have  dis- 
appeared on  recovery  from  the  disease.  In  a  third  case  of  lymph- 
adenoma  of  the  lower  eyelid,  the  size  of  a  pigeon's  egg,  this  suppu- 
rated during  an  intercurrent  attack  of  erysipelas,  and  afterward 
disappeared  completely. 

Jauicke  and  Neisser  (u  Exitus  letalis  nach  Erysipelimpfung  bei 
inoperablem  Mamma-carcinom  und  microscopischen  Befund  des 
geimpften  Carcinoms,"  Centralblattf.  Chirurgie,  1884)  have  recorded 
a  death  from  the  erysipelas  thus  intentionally  produced,  in  a  case 
of  cancer  of  the  breast  beyond  the  reach  of  an  operation.  A  pure 
culture  was  used.  At  the  post-mortem  it  was  proved  that  the  neo- 
plasm had  almost  completely  disappeared,  and  the  microscopical 
examination  of  portions  that  had  remained  appeared  to  show  that 
the  tumor  cells  had  been  destroyed  through  the  direct  action  of  the 
microbes.  Biedert  (Vorlaufige  Heilung  eiuer  ausgebildeten  Sar- 
comwucherung  in  einem  Kinderkopf  durch  Erysipel,"  Deutsche 
med.  Zeitung,  1886,  No.  5)  saw  in  a  child  suffering  from  a  sarcoma 
involving  the  posterior  part  of  the  cavity  of  the  mouth  and  pha- 
rynx, the  left  half  of  the  tongue,  the  naso-pharyngeal  space  and 
the  right  orbit,  the  tumor  disappear  almost  completely  during  an 
attack  of  erysipelas.  Cases,  on  the  other  hand,  have  been  reported 


132  ERYSIPELAS. 

in  which  after  an  accidental  or  intentional  attack  of  erysipelas  the 
malignant  tumor  commenced  to  grow  rapidly,  Neelsen  ("Rapide 
Wucherung  nnd  Ausbreitung  eines  Mammacarcinoms  nach  zwei 
schweren  Erysipel-Anfallen  von  15  resp.  10  tagiger  Dauer," 
Centralblatt  f.  Chirurgie,  1884,  p.  729)  describes  a  case  of  carci- 
noma of  the  breast,  in  which  after  two  severe  attacks  of  erysipelas 
the  tumor  not  only  commenced  to  grow  faster,  but  at  the  same  time 
regional  infection  progressed  also  more  rapidly. 

Babtchinsky  (Bulletin  Medical,  1890)  made  the  accidental  dis- 
covery that  the  microbe  of  erysipelas  is  a  direct  antagonist  to  the 
virus  of  diphtheria.  His  son,  while  suffering  from  a  most  severe 
case  of  diphtheria,  was  suddenly  attacked  by  erysipelas.  This 
complication,  grave  of  itself,  seemed  to  hasten  the  fatal  termination 
of  the  case,  and  during  the  first  few  hours  of  the  eruption  the 
patient  was  much  worse.  But  the  next  day  the  symptoms  had 
much  improved,  and  the  patient  made  a  rapid  recovery.  Follow- 
ing this  indication,  Babtchinsky  inoculated  a  second  case  of  diph- 
theria with  a  culture  of  the  microbe  of  erysipelas  grown  on  agar- 
agar,  and  with  an  equally  happy  result.  Since  this  time,  of  four- 
teen cases  of  diphtheria  treated  with  these  inoculations,  twelve 
resulted  in  recovery,  and  as  in  the  two  cases  resulting  fatally  the 
inoculation  produced  no  effect,  these  negative  results  only  tend 
to  confirm  the  efficacy  of  the  curative  inoculations.  It  is  remarkable 
that  in  all  the  cases  where  erysipelas  was  produced  artificially  this 
disease  pursued  a  mild  course,  and  the  patients  recovered  rapidly 
from  both  diseases. 

Schwimmer  ("  Ueber  dem  Heilwerth  des  Erysipels  bei  verschie- 
denen  Krankheitsformen."  Wiener  med.  Presse,  No.  15,  16,  1888) 
gives  an  account  of  11  cases  of  lupus,  in  all  of  which  no  improve- 
ment was  observed  after  an  intercurrent  attack  of  erysipelas.  In 
a  case  of  keloid  an  attack  of  erysipelas  was  folio  wed  by  marked 
improvement,  and  in  a  case  of  lipoma  a  similarly  favorable  effect 
was  observed.  Syphilitic  lesions  he  saw  temporarily  improved, 
while  the  erysipelas  had  no  effect  in  permanently  influencing  the 
course  of  the  disease. 

Bruus  (Monatschrift  /.  prakt.  Derm.,  B.  viii.,  No.  4)  gives  an 
account  of  the  effect  of  erysipelas  on  tumors  in  22  patients. 
Amongst  these,  three  cases  of  sarcoma  were  permanently  cured. 
Two  cases  of  multiple  keloid  after  burns  were  also  cured.  In  four 
cases  of  lymphoma  of  the  neck  some  of  the  glands  disappeared  and 
some  became  smaller.  In  five  cases  the  erysipelas  was  artificially 
produced  by  inoculation  with  a  pure  culture.  In  three  cases  of 
carcinoma  of  the  mamma  one  was  not  changed,  one  became  one-half 
smaller,  and  one  was  reduced  to  a  small  induration  in  the  scar  the 


RELATION  OF  ERYSIPELAS  TO   PUERPERAL   FEVER.      133 

size   of  a   pea.     A  multiple  fibre-sarcoma  was  greatly  benefited, 
while  an  orbital  sarcoma  was  not  improved. 

In  view  of  the  uncertainty  of  the  result,  and  the  danger  which 
attends  the  intentional  form  of  erysipelas,  the  danger  of  the  dis- 
ease being  as  great  as  in  the  accidental  form,  it  is  safe  to  predict 
that  no  further  inoculations  will  be  made  in  man  until  we  shall 
have  found  a  certain  antagonistic  action  of  the  streptococcus  of 
erysipelas  against  some  pathogenic  microbes  which  are  the  cause  of 
some  grave  disease  not  amenable  to  less  heroic  measures. 

MANNER  OF  INFECTION. — As  the  streptococcus  of  erysipelas 
produces  its  pathogenic  effects  in  the  lymphatic  vessels  and  diffuses 
itself  through  these  channels  in  the  tissues,  it  becomes  obvious  that 
infection  takes  place  as  soon  as  localization  is  effected  in  the  lym- 
phatic structures,  or  in  the  spaces  contributory  to  them.  Before 
antiseptic  surgery  was  practised,  infection  frequently  occurred 
through  accidental  or  intentional  wounds.  Even  before  the 
microbic  cause  of  erysipelas  was  known,  one  of  the  closest  of  clini- 
cal observers  (Trousseau)  claimed  that  infection  with  the  virus  of 
erysipelas  is  only  possible  through  some  wound  or  abrasion  of  the 
skin  ;  the  latter  may  be  so  insignificant  as  to  be  unnoticeable,  and 
entirely  overlooked  by  the  patient  and  physician.  Inoculation 
experiments  have  shown  that  the  time  of  incubation  is  from  fifteen 
to  sixty-one  hours,  so  that  we  can  estimate  the  time  quite  accurately 
in  a  case  of  beginning  erysipelas  when  the  infection  occurred. 
In  most  instances  infection  takes  place  through  some  wouud,  a 
slight  abrasion  of  the  skin,  which  may,  perhaps  never  have  attracted 
the  patient's  attention,  and  which  has  become  invisible  at  the  time 
the  disease  is  first  noticed.  Infection,  however,  may  also  take 
place  through  a  mucous  surface,  through  which  the  microbes  enter 
the  tissue  in  the  same  manner,  and  under  the  same  conditions  as 
when  infection  takes  place  through  the  skin.  One  of  the  severest 
cases  of  erysipelas  that  ever  came  under  my  observation  commenced 
in  the  pharynx,  or  tonsils,  and  as  the  symptoms  subsided  here,  a 
typical  and  severe  facial  erysipelas  developed.  The  patient  was 
suffering  at  the  time  from  secondary  syphilis. 

Relation  of  Erysipelas  to  Puerperal  Fever. 

Obstetricians  recognized  the  danger  of  exposing  puerperal 
women  to  the  infection  which  might  emanate  from  erysipelatous 
patients,  long  before  the  tangible  contagion  of  erysipelas  was 
known.  Since  the  discovery  of  Fehleisen,  this  subject  has  attracted 
renewed  attention,  and  positive  knowledge  has  accumulated  both 
from  accurate  clinical  observation,  and  from  the  fertile,  and  more 
positive  field  of  experimentation. 


134  ERYSIPELAS. 

Gusserow  ("  Erysipel  u.  Puerperalfieber/'^lrc/Mv.  f.  Gryncikologie, 
1887,  p.  169)  asserted  upon  the  basis  of  aa  extensive  experience, 
that  no  direct  etiological  relations  exist  between  the  contagion  of 
erysipelas  and  puerperal  fever.  He  had  under  his  care  puerperal 
women  suffering  from  erysipelas  of  the  skin  without  any  serious 
disturbances  following  in  the  genital  tract.  In  ten  other  cases,  one 
of  them  occuriug  during  an  epidemic  of  puerperal  fever,  the  ery- 
sipelas was  observed  as  a  complication  of  septic  affections  of  the 
genital  organs.  Gusserow  asserts  that,  in  this  case,  it  cannot  be 
claimed  that  the  erysipelas  could  have  caused  the  puerperal  affec- 
tion, as  the  latter  preceded  the  former.  But  another  point  could 
be  raised,  as  it  might  be  claimed  that  the  septic  processes  should  be 
made  answerable  for  the  occurrence  of  erysipelas.  The  author  has 
studied  this  subject  also  by  way  of  experiment.  A  pure  culture  of 
the  streptococcus  erysipelatosus,  which  had  been  tested  and  found 
reliable  in  producing  erysipelas  by  the  usual  methods  of  inocula- 
tion, was  injected  into  the  peritoneal  cavity  of  two  rabbits ;  in  two 
others  it  was  applied  to  an  open  wound  of  the  abdomen,  and  in  the 
last  two  animals  it  was  injected  into  the  subserous  connective  tissue 
of  the  peritoneum.  In  all  of  these  animals  no  effect  was  produced, 
and  no  pathological  changes  were  detected  at  the  point  of  injection 
when  the  animals  were  killed  some  time  after  the  inoculation. 
Gusserow  looks  upon  the  results  of  these  experiments,  if  not  as 
positive  proof,  nevertheless  as  strong  evidence  against  the  claim 
that  erysipelas  can  cause  puerperal  sepsis. 

Winckel  ("  Zur  Lehre  von  dem  internen  puerperalen  Erysipel," 
VerTi.  der  Deutschen  Gesellschaft  f.  Gyndkologie,  1  Congress,  p.  78), 
an  equally  reliable  and  able  observer,  has  come  to  entirely  opposite 
conclusions.  He  cultivated  from  a  parametric  abscess  which  had 
developed  after  childbed,  Fehleisen's  streptococcus.  Injections  of 
this  culture  in  rabbits  produced  typical  erysipelas.  The  same 
author  also  observed  erysipelas  following,  in  a  puerperal  woman 
suffering  from  suppurative  peritonitis,  pleuritis,  and  metro-lymph- 
angitis. The  patient  died  on  the  thirteenth  day.  The  starting- 
point  of  the  erysipelas  could  be  traced  to  an  ulcer  of  the  vulva. 

Blood  taken  from  the  right  side  of  the  heart  soon  after  death  was 
inoculated  upon  a  solid  nutrient  medium  and  produced  a  culture  of 
the  streptococcus  of  erysipelas.  The  same  culture  was  obtained  by 
inoculations  with  fluids  taken  from  the  peritoneal  and  pleural  cavi- 
ties, the  uterus,  kidneys,  and  liver.  In  three  cases  a  culture  thus 
obtained  was  injected  into  the  peritoneal  cavity  of  rabbits  and  no 
peritonitis  followed.  In  one  experiment  it  produced  suppurative 
peritonitis.  Guinea-pigs  proved  less  susceptible  to  infection  than 
rabbits.  In  white  mice  the  inoculations  were  invariably  followed 
by  a  fatal  disease.  From  the  results  of  these  experiments,  the 


KELATION    TO    PHLEGMONOUS    INFLAMMATION.       135 

author  claims  that  the  virus  of  erysipelas  is  one  of  the  most  viru- 
lent puerperal  poisons,  and  believes  that  they  prove  the  causal  rela- 
tions of  erysipelas  to  puerperal  sepsis. 

Doyen  (British  Medical  Journal,  1888,  ix.  93,  has  also  found,  both 
in  mild  and  severe  cases  of  puerperal  fever,  a  streptococcus  similar 
to  the  one  described  by  Rosenbach  and  Fehleisen.  He  made  some 
inoculations  to  determine  their  relationships.  The  streptococcus 
found  in  the  lesions  of  puerperal  fever  caused  erysipelas,  and  the 
streptococcus  found  in  erysipelas  developed  puerperal  fever.  The 
author  believes  that  the  microbe  of  puerperal  sepsis  is  the  same  as 
that  of  erysipelas. 

Puerperal  sepsis  from  the  virus  of  erysipelas  can  only  be  feared 
when  the  virus  is  brought  in  contact  with  an  absorbing  surface  in 
the  genital  tract,  but  when  this  takes  place  and  the  streptococci 
reach  the  enlarged  lymphatic  vessels  of  the  puerperal  uterus,  the 
most  violent  and  fatal  form  of  puerperal  sepsis  is  almost  certain  to 
follow. 

Relation  of  Erysipelas  to  Phlegmonous  Inflammation  and 
Suppuration. 

Some  difference  of  opinion  still  exists  among  pathologists  with 
regard  to  the  question  whether  the  streptococcus  of  erysipelas  pos- 
sesses pyogenic  properties.  The  majority  of  those  who  have  studied 
this  subject  experimentally  deny  this,  and  assert  that  when  suppura- 
tion takes  place  in  cases  of  erysipelas  it  is  the  result  of  a  secondary 
infection  with  pus-microbes,  and,  on  this  account,  look  upon  phleg- 
monous  inflammation  as  a  complication,  and  not  as  a  condition 
belonging  to  the  erysipelatous  process. 

Hajeck  ("  Das  Verhaltniss  des  Erysipels  zur  Phlegmone,"  Deutsche 
med.  Wochenschrift,  1886,  No.  47)  has  made  careful  investigations 
to  show  that  the  streptococcus  of  erysipelas  is  neither  in  form  nor 
culture  materially  different  from  the  streptococcus  pyogenes,  but  he 
showed,  also,  that  in  fifty-one  cutaneous  or  subcutaneous  inocula- 
tions with  a  pure  culture  of  the  streptococcus  of  erysipelas  in  rab- 
bits, the  result  was  always  a  superficial  migrating  dermatitis  which 
resembled  to  perfection  erysipelas  in  man,  while  similar  injections 
with  the  streptococcus  pyogeues  produced  a  more  intense  and  deeply 
seated  inflammation,  which  in  almost  every  instance  terminated  in 
suppuration.  The  difference  in  the  action  of  the  two  microbes  on 
the  tissues  plainly  demonstrated  their  non-identity.  Microscopical 
examination  of  the  inflamed  tissues  showed  a  still  more  important 
difference  as  far  as  the  localization  and  local  diffusion  of  the  microbes 
were  concerned.  The  coccus  of  erysipelas  was  always  found  with 
the  products  of  inflammation  within  the  lymphatic  vessels,  and  only 


136  ERYSIPELAS. 

exceptionally  in  the  connective-tissue  spaces,  which  anatomically 
are  only  a  part  of  the  lymphatic  system.  The  streptococcus  pyo- 
genes  penetrates  the  tissues  more  deeply ;  it  is  not  only  found  in 
the  lymphatic  vessels,  and  connective-tissue  spaces,  but  it  migrates 
beyond  the  lymphatic  system  and  infects  different  kinds  of  tissue, 
thus  giving  rise  to  a  more  deeply  seated  and  more  intense  inflam- 
mation. The  cocci  of  erysipelas  are  found  only  exceptionally  in 
the  immediatete  vicinity  of  bloodvessels,  while  the  streptococcus  of 
suppuration  can  always  be  seen  arranged  in  radiate  lines  around 
vessels  entering  the  adveutitia,  the  muscular  coat,  and  often  even  in 
the  lumen  of  the  vessel.  In  man,  the  same  histological  differences 
can  be  seen  in  erysipelas  and  phlegmonous  inflammation  as  in  the 
artificial  conditions  in  animals  subjected  to  experiment,  and  the 
same  pathological  differences  are  also  constantly  found.  The  author 
asserts  that  Fehleisen  was  in  error  when  he  claimed  that  the  forma- 
tion of  abscesses  occurred  independently  of  the  erysipelatous  infec- 
tion. He  affirms  that,  in  rabbits  inoculated  with  the  virus  of 
erysipelas  after  the  acute  inflammation  has  subsided,  circumscribed 
small  nodules  which  remain  may  suppurate,  but  the  suppurative 
process  remains  circumscribed,  while  after  injection  with  cultures 
of  the  streptococcus  pyogenes  the  inflammation  assumes  a  phleg- 
monous type,  and  the  suppuration  is  always  more  diffuse.  Under 
certain  circumstances,  a  circumscribed  subcutaneous  suppuration 
can  also  take  place  in  erysipelatous  inflammation  in  man.  When 
suppuration  in  a  joint  takes  place,  however,  it  is  not  caused  by  the 
erysipelatous  infection,  but  is  due  to  the  presence  of  pus-microbes. 
Death  following  erysipelas  is  caused  by  the  introduction  into  the 
blood  of  ptomaines  in  sufficient  quantity  to  produce  fatal  intoxica- 
tion, or  by  the  entrance  of  the  cocci  into  the  circulation,  which 
seldom  takes  place,  or  it  results  from  complications  incident  to  the 
disease  occurring  independently  of  it.  In  the  discussion  on  this 
paper  Eiselsberg  said,  from  the  knowledge  he  derived  from  his  own 
personal  experimental  work,  he  would  agree  with  Passet  in  that  the 
streptococcus  erysipelatosus  and  pyogenes  do  not  differ  in  their 
pathogenic  effects.  They  are  not  different  species  of  microbes,  but, 
at  the  most,  only  varieties  of  the  same  species.  Passet  found  that 
the  streptococcus  which  he  cultivated  from  a  phlegmonous  abscess 
was  different  from  the  one  described  by  Rosenbach,  inasmuch  as  in 
culture  it  resembled  the  coccus  of  erysipelas. 

Von  Noorden  ("Ueber  das  Vorkommen  von  Streptococcen  im 
Blut  bei  Erysipel,"  Milnchener  med.  Woehenschrift,  No.  3,  1887) 
records  an  observation  which  tends  to  prove  that  the  coccus  of  ery- 
sipelas occasionally  enters  the  circulation,  and  that,  when  it  localizes 
in  distant  parts  of  the  body,  it  can  produce  suppuration.  In  the 
course  of  a  severe  attack  of  erysipelas  which  proved  fatal,  suppura- 


KELATION    TO    PHLEGMONOUS    INFLAMMATION.       137 

tion  of  the  sheaths  of  the  tendons  of  the  hand  occurred.  Soon 
after  death  blood  was  taken  from  the  heart,  and  with  it  a  solid 
nutrient  medium  was  inoculated,  with  the  result  of  producing  a 
culture  which  in  every  respect  resembled  the  streptococcus  of  ery- 
sipelas. 

Simoue  observed  a  case  of  pyaemia  which  developed  in  a  patient 
suffering  from  erysipelas,  and  the  bacteriological  study  of  this  case 
led  him  to  assert  that  the  streptococcus  of  suppuration  and  of  ery- 
sipelas were  the  same.  His  experiments  on  animals  with  both 
organisms  yielded  the  same  results. 

Rheiner  ("  Beitrage  zur  pathologischen  Anatomic  des  Erysipels 
bei  Gelegenheit  der  Typhus-epidemie  in  Zurich,"  1884,  Virchow's 
Archiv,  B.  c.  S.  185)  found  Fehleisen's  streptococcus  in  all  cases  of 
traumatic  erysipelas  which  he  examined,  but  was  unable  to  find  it 
in  two  cases  of  gangrenous  erysipelas  following  typhus.  In  these 
cases  he  found  bacilli  which  he  believed  were  identical  with  Klebs- 
Eberth's  bacillus  of  typhus. 

Max  Wolff  ("  Bacterienlehre  bei  accidentellen  Wund-Krank- 
heiten,"  VirchoVs  Archiv,  B.  Ixxxi.  S.  408),  from  a  review  of  this 
subject,  and  a  number  of  original  observations,  came  to  the  conclu- 
sion that  certain  micrococci  produced  some  chemical  poison  which 
occasioned  erysipelas. 

The  distinction,  moreover,  between  erysipelas  and  phlegmonous 
processes  was  formerly  not  accurately  made,  and  Till  man  ns  even 
believed  that  the  germs  of  erysipelas  could  produce  septic  disease. 

To  complicate  this  subject  still  more,  Bonome  and  Bordini  (Cen- 
tralblattf.  Chirurgie.,  No.  7,  1887)  claim  that  they  have  found  the 
staphylococcus  in  two  cases  of  erysipelas.  The  authors  assert  that 
in  the  fluid  removed  from  the  bullse  of  a  case  of  facial  erysipelas 
they  found  the  staphylococcus  pyogenes  aureus  and  no  streptococci. 
Culture  experiments  were  made,  and  the  product  was  a  luxuriant 
growth  of  the  yellow  coccus.  Inoculations  in  rabbits  yielded 
positive  results  with  recovery. 

The  second  case  was  one  of  phlegmonous  erysipelas  of  the  face, 
from  which  they  cultivated  the  staphylococcus  pyogenes  citreus. 
Inoculations  with  this  culture  were  again  followed  by  positive 
results.  From  these  observations  the  authors  conclude  that  other 
microorganisms  than  the  streptococcus  of  Fehleisen  can  produce 
erysipelas.  At  a  recent  meeting  of  the  Academy  of  Medicine  in 
Paris,  Doyen  read  a  paper  on  the  relations  existing  between  ery- 
sipelas and  puerperal  fever.  By  means  of  clinical  observations 
and  experimental  inoculations  the  author  claimed  to  have  demon- 
strated that  the  puerperal  streptococcus,  which  is  the  microorganism 
characteristic  of  that  affection,  almost  always  produces  erysipelas 
and  a  small  abscess  in  the  rabbit.  In  women,  it  often  produces 


138  EKYSIPELAS. 

erysipelas,  phlegmonous  inflammation,  or  purulent  pleuritis.  The 
streptococcus  of  erysipelas  produces  the  disease  in  rabbits  almost 
invariably,  and  sometimes  phlegmons  or  peritonitis  in  man.  The 
streptococcus  of  pus  sometimes  produces  erysipelas  in  the  rabbit. 
These  three  streptococci  are  similar  in  cultures  and  appear  to  be 
one  and  the  same  whose  manifestations  may  vary. 

Smirnoff  found  in  one  case  of  erysipelas  the  specific  microbe  in 
the  metacarpo-phalangeal  joints  of  the  left  hand  which  was  the  seat 
of  the  disease.  In  the  case  of  a  man  who  had  died  of  erysipelas 
enormous  colonies  of  the  streptococcus  were  found  in  the  right 
shoulder  and  knee-joints.  The  synovia!  fluid  injected  into  rabbits 
occasioned  erysipelas  migrans. 

Verneuil  and  Clado  ("  De  PIdentite  de  PErysipele  et  de  la 
Lymphangite-aigue,"  Compt.  rend.,  T.  108,  No.  14)  found  in  the 
pus  of  four  cases  of  typical  suppurative  lymphangitis  only  the 
cocci  of  erysipelas,  and  by  inoculations  with  them  produced  ery- 
sipelas artificially  in  rabbits.  The  authors  consequently  came  to 
the  conclusion  that  erysipelas  and  lymphangitis  are  only  two  forms 
of  one  and  the  same  acute,  infectious,  parasitic  disease. 

Kahlden  (Centralblatt  f.  Bacteriologie  und  Parasiten-kunde,  B.  i. 
S.  22),  after  a  careful  study  of  the  recent  literature  on  erysipelas 
and  the  difference  in  opinion  on  the  pathogenic  properties  of  the 
streptococcus  erysipelatosus,  remarks  that  the  subtility  in  the  differ- 
ences between  the  morphology  and  the  cultures  of  the  microbe  of 
erysipelas  and  the  streptococcus  of  suppuration  are  undoubtedly 
the  reason  why  no  uniformity  of  opinion  exists  in  regard  to  their 
specific  pathogenic  effects,  especially  as  to  the  possibility  of  Fehlei- 
sen's  streptococcus  producing  suppuration.  To  this  I  might  add 
that  not  every  superficial  diffuse  inflammation  of  the  skin  is  ery- 
sipelas, and  not  every  abscess  occurring  during,  or  soon  after,  an 
attack  of  erysipelas  should  be  considered  as  a  product  of  this 
disease.  The  surgeon  will  do  well  to  hold  to  the  teachings  of 
Fehleiseu,  until  more  convincing  proof  shall  have  been  furnished 
of  the  pathogenic  identity  of  the  streptococcus  of  erysipelas  and 
the  streptococcus  of  suppuration. 


CHAP  TEE    XIII. 

ERYSIPELOID. 

A  NEW  form  of  infective  dermatitis,  which  in  many  respects 
resembles  erysipelas,  has  been  recently  described  by  Rosenbach 
("  Ueber  das  Erysipeloid,"  Archiv  f.  klin.  Chirurgie,  B.  xxxvi. 
Heft  2)  under  the  name  of  erysipeloid.  It  attacks  usually  the 
fingers  and  exposed  portion  of  the  hand,  and  is  most  frequently 
met  with  in  persons  who  handle  game  or  dead  animals,  as  cooks, 
butchers,  fish-dealers,  and  tanners.  The  affection  starts  from  some 
minute  abrasion  of  the  skin,  as  a  bluish-red  infiltration  which 
slowly  advances  in  a  proximal  direction.  The  inflamed  parts  are 
the  seat  of  a  burning,  smarting  sensation.  While  the  skin  at  the 
point  of  infection  returns  to  its  natural  condition  and  color,  the 
zone  of  infiltration  becomes  larger  as  it  continues  to  spread  until 
the  disease  appears  to  exhaust  itself  in  the  course  of  from  one  to  three 
weeks.  The  infectious  material  is  contained  in  decomposing  animal 
substances.  The  infection  may  take  place  in  any  abraded  part  of 
the  body  which  comes  in  contact  with  material  containing  the  virus. 
The  general  health  is  not  affected  and  the  temperature  remains 
normal.  The  disease  travels  very  slowly,  so  that  if  infection  takes 
place  in  the  tip  of  a  finger,  it  reaches  the  metacarpus  in  about  eight 
days,  and  during  the  next  eight  days  it  spreads  over  the  back  of 
the  hand,  from  where  an  adjacent  finger  may  become  infected,  the 
extension  then  taking  a  direction  opposite  to  the  lymph  current. 
Repeated  experiments  to  obtain  a  culture  failed,  until  in  November, 
1886,  the  author  succeeded  in  cultivating  it  upon  gelatin  from  a  case 
in  which  the  disease  could  be  traced  to  infection  from  old  cheese. 
The  author  injected  a  pure  culture  under  the  skin  of  his  own  arm 
at  three  different  points.  After  forty-eight  hours  he  experienced  a 
smarting,  burning  sensation  at  the  points  of  injection,  at  the  same 
time  a  circumscribed  redness  appeared  around  each  puncture,  which 
soon  became  confluent.  On  the  fifth  day  each  puncture  was  sur- 
rounded by  a  zone  of  inflammation  the  size  of  a  silver  dollar, 
somewhat  elevated  above  the  uiveau  of  the  surrounding  skin. 
While  the  centre  of  this  red  patch  became  pale,  the  zone  of  inflam- 
mation continued  to  enlarge.  In  the  inflamed  area  the  capillary 
vessels  could  be  seen  enlarged,  presenting  in  the  zone  an  arterial  hue 
with  a  slight  tinge  of  brown,  while  inside  of  the  zone  the  color  was 


140  ERYSIPELOID. 

a  livid  brown.  In  the  skin  which  returned  to  its  normal  pale  color, 
slight  suggillatious  appeared  as  though  some  of  the  red  blood- 
corpuscles  in  the  tissues  had  been  destroyed  during  the  progress  of 
the  disease.  The  disease  appeared  to  have  completely  subsided  on 
the  eighth  day,  when  the  same  smarting  sensations  returned,  and  a 
new  zone  appeared  around  the  old  one,  On  the  tenth  day  the  area 
measured  in  its  transverse  diameter  twenty-four  centimetres,  and  in 
the  parallel  direction  of  the  arm  eighteen  centimetres.  After  this 
the  affection  disappeared  permanently.  During  all  this  time  the 
general  health  remained  unimpaired,  and  the  temperature  varied 
from  36.8°  to  37.2°  C.  (98.2°  to  99°  F.).  A  microscopical  exami- 
nation of  the  pure  culture  showed  that  it  was  composed  of  swarms 
and  heaps  of  irregular,  round  and  elongated  bodies  larger  than  the 
staphylococci.  The  author  first  believed  that  these  bodies  were 
cocci,  but  later  he  saw  a  network  of  intertwining  threads  and 
decided  that  they  were  thread-forming  microbes.  In  old  cultures, 
the  threads  were  very  abundant  and  arranged  in  every  possible  way 
and  direction.  These  threads  looked  as  though  branches  were 
given  off,  but  on  closer  examination  it  could  be  seen  that  no  organic 
connection  existed  between  them.  Terminal  spores  at  the  tips  of 
the  threads  were  numerous  and  could  not  be  stained.  Neither  the 
microbe  nor  the  threads  manifested  motile  power  in  the  culture,  or 
when  suspended  in  water.  A  gelatin  culture  became  visible  on 
the  fourth  day  as  a  delicate  cloud  which  increased  in  size  very 
slowly  at  a  temperature  of  20°  C.  (68°  F.).  The  older  cultures 
change  into  a  brownish-gray  color,  and  then  resemble  the  culture 
of  the  bacilli  of  mice  septicaemia.  In  cultures  four  months  old  the 
growth  was  not  entirely  suspended. 

The  author,  as  yet,  has  not  given  a  name  to  this  microbe,  but* 
believes  that  it  belongs  to  the  "cladothrix"  variety  of  microorgan- 
isms.    He  wished  to  ascertain  the  action  of  this  microbe  on  lupus, 
but  in  several  cases  in  which  it  was  tried  the  inoculations  failed. 


CHAPTEE   XIV. 

NOMA. 

THE  most  violent  of  the  local  effects  of  bacteria  are  seen  in 
various  affections  which  terminate  in  gangrene,  such  as  traumatic 
gangrene  and  noma.  Here,  it  is  not  a  case  of  death  of  the  tissues 
as  the  result  of  violent  inflammation,  so  much  as  a  direct  killing  of 
them  by  the  ptomaines  of  the  bacteria.  In  acute  progressive  gan- 
grene, bacilli  have  been  found  which  are  apparently  the  cause  of 
the  disease.  In  noma,  long  bacilli  are  present,  which  Lingard 
has  demonstrated  to  be  the  cause  of  the  disease.  In  gangrenous 
stomatitis  in  the  calf,  which  affects  this  animal  at  particular  seasons, 
he  has  found  bacilli  which  are  very  similar  in  appearance  to  those 
present  in  noma  in  man.  On  cultivation  they  present  characters 
which  render  them  easily  distinguishable  from  other  bacteria,  and 
on  inoculation  of  these  organisms  into  the  calf  a  gangrenous  sto- 
matitis is  again  produced. 

Rauke's  ("  Etiology  and  Pathological  Anatomy  of  Gangrene 
resulting  from  Noma,"  Archives  of  Pediatrics,  April,  1888)  inves- 
tigations on  noma  led  to  the  following  conclusions  :  Different  forms 
of  gangrene  resulting  from  noma  can  unquestionably  occur  sponta- 
neously in  children  who  have  a  tendency  to  disease  of  this  character 
— that  is,  without  contact  with  other  cases  of  noma.  The  frequent 
occurrence  of  cases  of  noma  in  public  institutions,  and  the  apparent 
preference  of  the  disease  for  localization  upon  the  mucous  membrane 
of  the  different  openings  of  the  body,  suggest  that  the  origin  of  it 
may  be  referred  to  the  penetration  from  without  of  microorganisms. 
In  the  zone  of  tissue  contiguous  to  that  which  has  undergone 
necrosis  from  noma  may  be  found  cocci  which  have  almost  the 
characteristics  of  a  pure  culture.  At  the  periphery  of  the  necro- 
biotic  zone  which  has  been  invaded  by  cocci  the  connective-tissue 
is  found  to  be  in  an  active  state  of  nuclear  proliferation.  The 
entire  condition  is  suggestive  of  the  tissue  necrosis  in  field  mice, 
which  is  caused  by  a  chain  coccus,  and  has  been  described  by  Koch. 
Up  to  the  present  time  the  specific  nature  of  the  cocci  which  are 
found  in  noma  has  not  been  shown.  In  the  tissues  which  limit 
the  necrotic  areas  are  found  peculiar  degenerative  processes  in  the 
nuclei  which  in  some  cases  suggest  karyokinesis.  These  changes 
in  the  nuclei  appear  to  belong  to  necrosis  in  general. 


CIIAPTEK   XV. 


TETANUS. 

HISTORY. — The  infectious  nature  of  tetanus  was  well  known 
and  established  before  the  discovery  of  the  bacillus  tetani.  In 
1859  Betoli  related  the  case  of  a  bull  that  died  of  tetanus  after 
castration.  Several  slaves  ate  some  of  the  flesh  of  the  dead  animal 
and  of  these,  three  were  in  a  few  days  seized  with  tetanus,  two  of 
them  dying.  He  adds  further  that  in  Brazil,  where  this  occurred, 
the  flesh  of  animals  dead  of  tetanus  is  generally  regarded  as  capa- 
ble of  transmitting  the  disease.  In  1870  Anger  reported  a  case  in 
which  a  horse  had  spontaneous  tetanus,  after  which  three  puppies 
which  had  been  in  the  same  stable  were  also  affected.  Kelly  in 
1873  had  three  cases  in  the  same  week,  all  arising  in  a  civil  hospi- 
tal, and  a  few  days  later  there  was  a  fourth  case  in  a  neighboring 
hospital. 

Larger  in  1853  saw  a  woman  who  had  a  fall  while  cleaning  a 
farm-yard,  causing  a  slight  wound  of  the  elbow.  Four  weeks 
later,  she  was  seized  with  tetanus,  and  on  investigation  it  was  found 
that  a  horse  affected  with  that  disease  had  been  in  a  stable  opening 
into  the  yard  where  she  fell.  He  also  mentions  that  in  a  small 
village  where  tetanus  was  previously  unknown,  five  cases  appeared 
in  eighteen  months  under  quite  different  climatic  conditions.  Of 
these,  one  had  been  taken  to  a  hospital,  after  which  two  others  in 
the  same  ward  became  affected. 

Verhoogen  and  Baert  have  recently  published  an  article  upon 
the  nature  and  etiology  of  tetanus,  in  which  these  authors  cite  the 
well-known  endemic  character  of  the  disease  in  our  Southern  States, 
Cuba,  Ceylon,  a  number  of  the  Pacific  Islands,  and  other  localities, 
and  quote  a  large  number  of  circumstances  that  suggest  the  occa- 
sional epidemic  type  of  the  affection  as  met  in  man  and  some  of 
the  lower  animals.  Among  a  number  of  clinical  and  experimental 
occurrences  suggesting  the  probability  of  the  transmissibility  of 
the  malady,  and  the  likelihood  of  the  agent  of  transmission  exist- 
ing in  unclean  instruments,  Thiriar's  experience  is  narrated.  This 
operator  was  unfortunate  enough  to  lose  ten  cases  of  major  opera- 
tions by  tetanus  before  he  determined  the  seat  of  the  infection  to 
exist  in  his  haemostatic  forceps,  the  thorough  sterilization  of  which 


CULTIVATION    EXPERIMENTS.  143 

by  heat  was  happily  followed  by  a  complete  cessation  of  the  unde- 
sirable sequences. 

Although  the  infectious  nature  of  tetanus  was  suspected  for  a 
long  time,  it  is  only  quite  recently  that  the  real  microbic  cause  was 
discovered  almost  simultaneously  by  Nicolaier  and  Rosenbach. 
Nicolaier  showed  the  exogenous  origin  of  the  disease  by  finding  a 
bacillus  in  earth  which  produced  tetanus  in  animals  by  inoculation. 
Kosenbach  found  a  similar  bacillus  in  the  pus  of  a  patient  suffering 
from  traumatic  tetanus.  The  identity  of  the  bacillus  of  tetanus 
with  Nicolaier's  bacillus  of  earth  tetanus  was  demonstrated  in 
Koch's  laboratory  April  10,  1887. 

DESCRIPTION  OF  THE  BACILLUS  TETANI. — Rosenbach  describes 
the  bacillus  as  an  anaerobic  microorganism  which  presents  a  bristly 
appearance,  with  a  spore  at  one  of  its  extremities  which  gives  it  the 
resemblance  to  a  pin,  or  drumstick.  According  to  Kitasato,  the 


FIG. 


Tetanus  bacilli  bearing  spores  from  an  agar  culture.    X  1000. 
(FRANKEL  and  PFEIFFER.) 

bacilli  produce  spores  in  30  hours  in  cultures  kept  at  a  temperature 
of  the  body.  They  manifest  great  resistance  to  heat,  as  they  have 
been  found  active  after  an  exposure  of  one  hour  to  80°  C.  (176°  F.) 
moist  heat,  and  are  only  destroyed  by  placing  them  in  a  steam  appa- 
ratus heated  to  100°  C.  (212°  F.)  for  five  minutes.  The  bacillus  has 
been  found  in  different  kinds  of  soil  and  in  street  dust.  In  man,  it 
has  been  found  in  tetanic  patients  in  the  wound  secretions,  in  the 
nerves  leading  from  the  seat  of  infection,  and  in  the  spinal  cord. 

CULTIVATION  EXPERIMENTS. — Roseubach  found  it  impossible 
to   obtain  a  pure  cultivation ;  although  he  resorted  to  fractional 


144  TETANUS. 

cultivation,  it  was  found  that  the  last  culture  was  still  contaminated 
by  one  or  more  additional  microbes.  Fliigge  claimed  to  have 
obtained  a  pure  culture  by  heating  for  five  minutes  the  mixed  cul- 
ture to  100°  C.  (212°  F.),  but  after  this  procedure  the  bacillus  was 
incapable  of  further  propagation.  After  many  trials  it  was  found 
that  sterilized  solid  blood-serum  was  the  best  soil  for  the  propaga- 
tion of  the  bacillus  outside  of  the  body.  Both  Nicolaier  and 
Rosenbach  observed  the  anaerobic  nature  of  the  bacillus,  as  it  was 
found  impossible  to  obtain  a  culture  on  the  surface  of  the  nutrient 
media,  or  anywhere  else  where  oxygen  could  not  be  excluded.  The 
culture  appeared  slowly  as  a  delicate  whitish-gray  film  in  the  track 
of  the  needle  puncture  below  the  surface  of  the  culture  substance. 
By  a  long  series  of  cultivations,  Rosenbach  finally  succeeded  in 
eliminating  all  other  microbes  with  the  exception  of  a  bacillus  of 
putrefaction.  The  growth  of  the  bacillus  takes  place  most  readily 
at  an  equable  temperature  of  37°  C.  (98.6°  F.),  and  becomes  first 
visible  about  the  third  day  in  the  depth  of  the  culture  media. 

Kitasato  ("  Ueber  den  Tetanuserreger,"  Verh.  d.  Deutschen  Gesell- 
schaftf.  Chirurgie,  1889)  has  finally  succeeded  in  obtaining  a  pure 
culture  of  the  bacillus  of  tetanus  from  pus  taken  from  a  patient 
suffering  from  tetanus.  As  the  bacillus  will  only  grow  where 
atmospheric  air  is  excluded,  he  exposed  his  cultures  to  an  atmos- 
phere of  hydrogen  gas.  Mixed  cultures  which  had  been  kept  for 
several  days  in  the  incubator  were  then  exposed  for  half  an  hour 
to  an  hour  to  a  temperature  of  80°  C.  (176°  F.)  in  a  water-bath,  and 
further  growth  was  secured  upon  plate  cultures  in  closed  glass  vessels 
filled  with  hydrogen  gas.  He  succeeded  in  destroying  all  other  anae- 
robic bacilli  found  in  the  pus  by  heating  the  mixed  culture  to  80°  C. 
(176°  F.),  with  the  exception  of  the  bacillus  of  tetanus,  which  upon 
gelatin  plates  in  the  hydrogen  atmosphere  at  a  temperature  of  18°  to 
^0°  C.  (64.4°  F.  to  68°  F.)  after  a  week  produced  a  visible  culture. 
Growth  is  more  rapid  at  a  temperature  of  18°  to  20°  C.  (64.4°  F.  to 
68°  F.),  when  a  culture  appears  in  from  four  to  five  days,  and  if 
the  temperature  is  kept  at  36°  to  38°  C.  (95.8°  F.  to  100.4°  F.) 
the  development  of  spores  and  bacilli  takes  place  most  rapidly. 

INOCULATION  EXPERIMENTS. — Nicolaier  ("  Ueber  infectiosen 
Tetanus,"  Deutsche  med.  Wochenschrift,  1884,  No.  52)  produced 
tetanus  in  rabbits  and  mice  experimentally  by  inoculations  with 
different  kinds  of  earth.  Out  of  140  experiments,  in  69  a  disease 
was  produced  which  very  closely  resembled  tetanus  in  man.  In 
the  pus  at  the  point  of  inoculation  bacilli  and  micrococci  were  con- 
stantly found.  Among  the  bacilli  one  form  was  invariably  present ; 
this  bacillus  resembled  in  appearance  and  culture  the  bacillus  of 
septicaemia  in  mice,  but  was  more  slender.  This  bacillus  was  found 
in  isolated  places  in  the  connective-tissue,  but  could  not  be  found 
in  the  muscles,  nerves,  and  blood.  If  the  earth  was  sterilized  by 


INOCULATION    EXPERIMENTS.  145 

exposure  to  high  temperature  for  an  hour  the  inoculations,  without 
exception,  proved  harmless,  showing  conclusively  that  the  contagium 
of  tetanus  had  been  rendered  inert.  Inoculations  with  pus  taken 
from  tetanic  animals  were  most  successful.  Inoculations  with  mixed 
cultures  grown  in  solidified  blood-serum  yielded  positive  results 

Rosenbach  ("  Zur  Aetiologie  des  Wuudstarrkrampfs  beim  Men- 
schen,"  Laugenbeck's  Archiv,  B.  xxxiv\  S.  306)  made  his  experi- 
ments with  a  mixed  cultivation  grown  from  the  pus  taken  from 
the  line  of  demarcation  of  a  case  of  frost  gangrene  in  a  patient 
who  had  died  of  tetanus.  The  inoculations  proved  successful. 
Carle  and  Rattone  (Griornale  delta  R.  Academia  di  Med.  di  Torino, 
1884,  No.  3)  succeeded  in  producing  tetanus  in  rabbits  by  inocula- 
tion with  pus  from  a  suppurating  acne  in  a  tetanic  patient  in  whom 
the  infection  was  traced  to  this  source. 

Bonome  ("  Ueber  die  Aetiologie  des  Tetanus/'  Deutsche  med. 
Wochenschrift,  1887,  No.  15)  reports  the  case  of  a  man  suffering 
from  paraplegia,  the  result  of  disease  of  the  spine  in  the  dorsal 
region,  complicated  by  an  extensive  sacral  decubitus,  the  seat  of 
phlegmouous  purulent  inflammation,  who  was  suddenly  attacked 
by  tetanus,  which  proved  fatal  in  two  days.  One  hour  after  death 
a  small  portion  of  the  infiltrated  tissue  around  the  gangrenous  part 
was  removed,  and  after  reducing  it  to  a  fine  pulp  by  trituration,  he 
injected  it  under  the  skin  of  a  rabbit.  Twenty-two  hours  after  the 
inoculation  the  animal  died  with  well-marked  symptoms  of  tetanus. 
The  products  of  inflammation  from  the  point  of  injection  thrown 
into  the  subcutaneous  tissue  of  other  animals  produced  the  disease, 
while  intravenous  injections  proved  harmless.  The  gravity  of 
symptoms  following  subcutaneous  injections  was  commensurate 
with  the  quantity  of  fluid  injected.  Guinea-pigs  proved  less  sus- 
ceptible to  infection  than  rabbits.  In  the  pus  taken  from  the  dead 
tissue  he  found,  besides  the  usual  pus-microbes,  a  bacillus  which 
resembled  in  every  respect  the  one  described  by  Nicolaier  and 
Roseubach.  Hochsinger  (Centralblatt  f.  Bacteriologie  u.  Parasiten- 
kunde,  B.  ii.  Nos.  6,  7)  made  his  observations  on  a  case  of  tetanus 
which  proved  fatal  on  the  fifth  day.  The  day  before  the  patient 
died  blood  was  abstracted  from  a  vein  under  strict  antiseptic  precau- 
tions for  microscopical  and  bacteriological  study.  No  microorgan- 
isms could  be  found  in  it.  With  the  greatest  care  sterilized  solid 
blood-serum  was  inoculated  with  the  blood,  making  with  the  needle 
both  superficial  tracks  and  deep  punctures.  The  nutrient  medium 
was  kept  at  a  temperature  of  37°  C.  (98.6°  F.).  On  the  third 
day,  a  white  cloudy  streak  marked  the  direction  of  the  deep  punc- 
tures, while  the  superficial  plant  remained  sterile.  On  the  third 
day  a  portion  of  the  culture  was  removed  and  stained  with  aniline 
gentian,  and  submitted  to  microscopical  examination.  Delicate 

10 


146  TETANUS. 

bacilli  measuring  from  0.8  to  1.2  micromillimetres  in  length,  com- 
posed the  culture.  The  detection  of  the  bacillus  was  quite  difficult, 
and  its  growth  very  slow.  On  the  sixth  day  the  serum  around  the 
punctures  had  become  more  cloudy,  and  the  microscope  showed  that 
the  bacilli  were  present  in  greater  abundance.  From  this  time  on, 
the  cultivation  ceased  to  increase,  and  the  surface  of  the  nutrient 
medium  still  remained  sterile.  From  the  original  culture  five  other 
tubes  were  inoculated,  but  in  only  one  of  them  could  a  slight  culti- 
vation be  detected  on  the  fourth  day.  A  large  rabbit  was  infected 
by  injecting  blood  obtained  from  the  patient  during  life.  The 
blood  was  intimately  mixed  with  sterilized  water,  and  a  syringeful 
of  this  mixture  was  injected  under  the  skin  in  the  iliac  region,  and 
half  this  quantity  under  the  skin  of  the  left  thigh.  The  next  day 
the  animal  appeared  quite  ill,  and  was  unable  to  use  the  left  hind 
leg,  which  was  dragged  along  in  walking.  At  this  time  great  ner- 
vous excitability  was  observed,  the  exaggerated  reflex  symptoms 
being  especially  well  marked  in  the  posterior  extremities  which,  on 
the  slightest  touch,  were  thrown  into  clonic  spasms.  On  the  fol- 
lowing day  the  animal  was  found  dead.  A  few  hours  before  death 
well-marked  symptoms  of  tetanus  developed.  No  positive  results 
were  revealed  at  the  post-mortem  examination.  Injections  of  blood 
from  this  animal  produced  no  results  in  other  rabbits,  and  cultiva- 
tion experiments  were  equally  fruitless.  A  syringeful  of  inspis- 
sated blood  of  the  patient,  kept  for  three  weeks,  thrown  under  the 
skin  of  a  white  mouse,  was  followed  by  a  fatal  attack  of  tetanus, 
while  a  second  animal  inoculated  in  a  similar  manner  with  one-half 
of  this  quantity  remained  perfectly  well.  Fliigge  had  before 
observed  that  by  injecting  blood  from  animals  rendered  tetanic  by 
inoculation,  it  was  necessary  to  use  a  large  quantity  in  order  to 
reproduce  the  disease  in  other  animals,  and  even  by  doing  so  the 
result  was  not  always  satisfactory.  It  appears  from  the  experience 
of  these  authors  that  the  blood  of  tetanic  patients  possesses  greater 
toxic  properties  than  the  blood  of  animals  suffering  from  the  same 
disease.  Hochsiuger  also  made  experiments  with  the  cultivation. 
Eleven  days  after  establishing  the  primary  cultivation  he  injected 
a  syringeful  of  the  liquefied  turbid  nutrient  material  into  the  sub- 
cutaneous tissue  of  the  thigh  of  a  medium-sized  rabbit.  The  next 
day  the  reflexes  were  increased,  respiration  more  rapid,  and  the 
animal  appeared  otherwise  quite  sick.  On  the  third  day  the  poste- 
rior extremities  were  stiff,  the  animal  dragging  them  in  walking. 
Reflex  irritability  enormously  exaggerated.  On  the  fifth  day  the 
animal  died.  In  another  experiment  he  injected  the  primary  cul- 
ture, seventeen  days  old,  into  the  left  thigh  of  a  rabbit.  On  the 
fourth  day  the  left  hind  leg  was  stiff,  at  the  same  time  the  reflexes 
were  intensified.  On  the  following  day  both  hind  legs  were  stiff, 


INOCULATION    EXPERIMENTS.  147 

and  the  animal  dragged  itself  along  with  difficulty  on  the  front 
legs.  On  the  sixth  day  the  animal  appeared  more  sick,  and  two 
days  later  died  with  well-marked  symptoms  of  tetanus.  The  lique- 
fied nutrient  serum  in  the  glass  tube,  containing  the  only  secondary 
culture,  hypodermically  injected  in  another  rabbit,  produced  tetanus. 

These  experiments  appear  to  prove  conclusively  that  the  patient's 
blood  contained  the  essential  microbe  of  tetanus.  The  bacillus 
found  in  the  patient  and  in  the  "affected  animals  corresponded  in 
every  respect  with  the  bacillus  described  by  Roseubach.  In  rab- 
bits, Fliigge  estimated  the  stage  of  incubation  at  from  three  to  five 
days,  and  the  duration  of  the  illness  from  the  time  that  the  first 
symptoms  were  noticed  to  the  fatal  termination,  from  five  to  seven 
days. 

Beumer  ("  Ueber  die  Aetiologische  Bedeutung  der  Tetanus- 
bacillen,"  Berl.  klin.  Woehenschrift,  1887,  No.  31)  gives  an  accu- 
rate and  able  description  of  his  studies  in  two  cases  of  tetanus. 
The  first  case  occurred  in  a  mechanic,  who  injured  himself  under 
the  nail  of  the  right  middle  finger  with  a  splinter  of  wood.  Eight 
days  after  the  injury,  the  patient  having  had  but  slight  pain  in  the 
finger,  pains  appeared  in  the  neck  and  muscles  of  the  back.  The 
next  morning  spasms  of  the  muscles  of  the  cnest,  abdomen,  and  jaw 
developed.  These  attacks  occurred  at  intervals  of  an  hour  and  a 
half.  Four  days  later  the  lower  extremities  were  affected,  also  the 
upper,  but  in  a  less  degree.  The  right  middle  finger  was  slightly 
swollen.  An  incision  was  made,  and  the  foreign  body  removed, 
which  was  followed  by  the  escape  of  a  drop  of  pus ;  death  on  the 
fourth  day.  The  second  case  was  a  boy  six  and  a  half  years  old, 
who  was  brought  into  the  clinic  with  well-marked  symptoms  of 
tetanus,  and  who  lived  only  a  few  hours  after  his  admission.  The 
author  obtained  some  of  the  dust  and  splinters  of  wood  from  the 
place  where  the  mechanic  had  injured  himself,  and  inserted  small 
particles  under  the  skin  of  mice  and  rabbits.  In  all  experiments 
the  animals  were  attacked  with  tetanus  in  from  two  to  three  days 
after  inoculation,  and  died  during  the  third  or  fourth.  The  spas- 
modic contractions  were  always  noticed  first  in  the  muscles  nearest 
the  point  of  inoculation.  A  portion  of  the  sole  of  the  foot  was 
taken  from  the  boy,  and  small  fragments  of  it  inserted  into  the 
subcutaneous  tissue  of  six  mice.  In  all  of  these,  symptoms  of 
tetanus  appeared  after  two  days,  developing  gradually  into  general 
convulsions  and  death.  The  same  results  were  obtained  in  mice 
and  rabbits  by  inoculations  of  particles  of  dust  taken  from  the 
spot  where  the  boy  sustained  the  injury.  The  bacillus  of  tetanus 
was  found  in  the  wound  of  the  second  patient  Beumer  is  firmly 
convinced  that  a  direct  relationship  exists  between  the  bacillus 
described  by  Nicolaier  and  Rosenbach  and  the  cause  of  tetanus. 


148  TETANUS. 

At  a  meeting  of  the  Imperial  Royal  Society  of  Physicians  of 
Vienna  (British  Medical  Journal,  July  25,  1888)  Eiselsberg  gave 
an  account  of  a  case  of  tetanus  in  Billroth's  clinic:  A  woman, 
aged  forty,  drove  a  splinter  of  wood  into  the  palm  of  her  hand 
while  scrubbing  the  floor.  A  fragment  of  the  splinter  was  ex- 
tracted by  her  husband.  During  the  course  of  the  next  week 
an  abscess  formed  in  the  hand  ;  this  was  opened  by  the  attending 
physician.  On  the  twelfth  day  after  the  injury  the  woman  was 
admitted  into  Billroth's  clinic  with  typical  symptoms  of  a  severe 
attack  of  tetanus,  which  lasted  four  weeks.  She  afterward  re- 
covered to  a  great  extent,  and  was  discharged  at  her  own  request. 
At  that  time  she  still  presented  slight  contractions  of  the  affected 
limb.  Two  mouths  later  a  suppurating  fistula  formed,  and  a  small 
splinter  of  wood  came  away  in  the  discharge.  The  wound  then 
completely  healed,  and  the  patient  made  a  perfect  recovery. 
Eiselsberg  used  the  extracted  piece  of  wood  for  making  cultures. 
Two  rabbits  were  inoculated  with  the  culture  thus  obtained,  one  of 
which  succumbed  to  tetanus  on  the  sixth  day  after  inoculation, 
while  the  second  one,  which  was  inoculated  at  a  later  date,  showed 
marked  symptoms  of  tetanus,  such  as  increased  irritability,  trismus, 
pleurosthotonus,  etc. 

Giordano  ("  Contribute  all'  Eziologia  del  Tetano,"  Griorn.  delta 
Acad.  di  Med.  di  Torino,  1887,  Nos.  3,  4)  performed  his  experi- 
mental work  on  the  following  cases  of  tetanus  in  the  laboratory  of 
Perroueito.  The  patient  was  a  man  forty  years  old,  who  fell  from 
a  hayloft  upon  the  frozen  ground,  and  was  brought  to  the  hospital 
twenty  hours  later  with  a  complicated  fracture  of  the  forearm.  The 
wound,  which  was  covered  with  dirt,  was  enlarged,  drained,  and 
partly  closed ;  on  the  fourth  day  trismus,  and  on  the  seventh  day 
death  from  well-marked  tetanus.  Immediately  after  death,  blood 
was  taken  from  the  wound  of  the  median  nerve,  and  fragments  of 
a  thrombus  from  a  vein  of  the  affected  limb  were  also  removed  and 
preserved  in  sterilized  beef-tea.  A  piece  of  necrotic  tissue  from  the 
wound  contained  microbes,  but  not  the  bacillus  described  byNico- 
laier.  Inoculations  with  blood  and  fragments  of  internal  organs 
failed  to  produce  tetanus.  Inoculations  with  pus  from  the  wound 
and  fragments  of  thrombus  caused  tetanus  in  rabbits  and  guinea- 
pigs.  Small  fragments  of  straw  taken  from  the  place  where  the 
patient  fell,  inserted  under  the  skin  of  a  rabbit,  produced  tetanus 
in  three  days.  The  pus,  among  other  microbes,  contained  few  of 
the  characteristic  bacilli.  Injections  of  pus  taken  from  the  tetanic 
animal  produced  tetanus  in  other  rabbits.  Inoculations  with  tissue 
from  the  medulla  oblongata  did  not  cause  the  disease.  Successful 
inoculations  were  made  from  the  second  and  third  rabbits.  Injec- 
tions of  dust  taken  from  the  place  where  the  patient  was  injured, 


INOCULATION    EXPERIMENTS.  149 

suspended  in  water  caused  no  symptoms,  but  a  culture  from  it, 
six  days  old,  contained  the  bacilli,  and  when  injected  subcutaneously 
produced  the  disease.  From  the  absence  of  the  bacilli  in  the 
internal  organs,  he  concluded  that  this  microbe  does  not  permeate 
the  whole  body,  and  that  the  disease  owes  its  origin  to  absorption 
of  toxic  agents  from  the  wound. 

Ohlmuller  and  Goldschmidt  (u  Ueber  einen  Bakterienbefund 
bei  Menschlichem  Tetanus,"  Centrcdblatt  f.  die  ges.  Medicin,  1887, 
No.  31)  made  a  thorough  bacteriological  examination  of  a  case  of 
tetanus  following  complicated  fracture  of  the  right  thumb.  The 
disease  appeared  the  day  following  the  injury  and  resulted  in  death 
after  not  more  than  seventeen  hours.  Soon  after  death  inoculation 
experiments  were  made  with  blood  taken  from  the  heart  and  spleen 
and  pus  from  the  seat  of  fracture,  according  to  directions  given  by 
Bumm.  The  cultivations  were  made  in  solid  blood-serum  and 
kept  at  a  temperature  of  38°  C.  (100.7°  F.).  The  tubes  con- 
taining blood  from  the  heart  and  spleen  remained  sterile,  but  the 
nutrient  media  infected  with  pus  showed  signs  of  growth  by  lique- 
faction of  the  solid  serum.  The  bacilli  which  were  detected 
resembled  those  of  mouse  septicaemia,  only  somewhat  larger  in  size. 
In  addition  to  these  microbes  streptococci  and  a  thicker  bacillus 
were  found.  Twenty-four  hours  later  liquefaction  had  increased, 
but  the  streptococci  had  diminished  in  number.  The  characteristic 
bacilli  were  pin-rods  with  globular  ends,  and  club-shaped  rods  with 
colorless  terminal  spores.  On  the  third  day  the  serum  had  under- 
gone more  advanced  liquefaction  and  at  the  same  time  a  fetid  odor 
was  noticed.  A  slide  compared  with  one  prepared  by  Nicolaier 
showed  the  identity  of  the  two  microbes.  In  order  to  prove  still 
further  their  identity  two  mice  were  inoculated  with  the  mixed  cul- 
tivation. Twelve  hours  after  infection  tetanus  had  made  its 
appearance,  followed  by  death  in  seventeen  hours.  It  should  be 
remarked  that  the  spasms  commenced  in  the  tail,  extended  to  the 
posterior  extremities,  and  then  gradually  forward.  From  these 
animals  blood-serum  was  taken  with  which  other  mice  were  infected. 
Again  tetanus  was  produced  and  successful  cultivations  were 
made.  Successive  cultivations  appeared  to  diminish  the  intensity 
of  the  virus.  Of  two  mice  of  equal  size  and  age,  one,  which 
received  one  portion,  died  of  tetanus  on  the  ninth  day,  while  the 
other,  which  received  a  dose  three  times  as  large,  died  on  the  third 
day.  Cultivations  on  agar-agar  always  remained  sterile.  Cultiva- 
tions in  sterilized  coagulated  albumen  from  chicken's  and  goose- 
eggs  showed  that  the  bacilli  retained  their  properties  for  about  a 
week,  but  later  they  were  displaced  by  other  organisms.  An 
attempt  was  made  to  destroy  the  other  microorganisms  by  heating 
the  mixed  cultivation  to  100°  C.  (212°  F.)  for  five  minutes.  The 


150  .TETANUS. 

result  was  satisfactory,  inasmuch  as  inoculations  produced  positive 
results  in  mice  and  blood-serum.  Inoculations  of  these  cultures 
into  a  ten  per  cent,  peptone  gelatin  medium  caused  rapid  liquefac- 
tion, and  the  microscope  showed  thicker  rods  with  long  processes. 
In  some  cultures,  bacilli  of  tetanus  were  found  as  late  as  the  ninth 
day.  Inoculation  with  the  last  cultures  had  no  effect.  He  ascer- 
tained also  that  inoculations  with  earth  had  so  often  failed  because 
not  enough  material  was  used.  He  made  additional  experiments 
using  a  much  larger  quantity.  The  first  experiment,  in  which  a 
portion  of  earth  half  the  size  of  a  pea  was  inserted  under  the  skin 
on  the  back,  was  successful.  After  twelve  hours  the  mouse 
sickened,  in  twenty  hours  presented  typical  evidences  of  tetanus, 
and  died  soon  afterward.  In  the  pus  at  the  seat  of  inoculation 
cocci  and  bacilli  of  tetanus  were  found  in  abundance  and  inocula- 
tion with  the  product  of  inflammation  produced  tetanus  as  surely  as 
pus  taken  from  wounds  of  tetanic  patients.  The  same  earth  ex- 
posed for  half  an  hour  to  an  hour  to  the  action  of  steam  was  ren- 
dered sterile  and  inoculations  with  it  proved  harmless. 

Of  the  greatest  scientific  and  practical  interest  are  the  observa- 
tions made  by  Bouome  (u  Ueber  die  Aetiologie  des  Tetanus," 
Fortschritte  der  Medicin,  1887,  No.  21)  in  reference  to  the  causation 
of  tetanus  by  infection  with  earth  containing  the  bacillus  discovered 
by  Nicolaier.  He  had  an  opportunity  to  observe  a  number  of  cases 
of  tetanus  after  the  recent  earthquake  at  Bajardo.  Of  the  seventy 
persons  injured  in  the  ruins  of  the  church,  seven  were  attacked  by 
tetanus.  From  bacteriological  investigations  in  connection  with 
these  cases,  he  came  to  the  same  conclusions  in  regard  to  the  cause 
of  the  disease  as  Nicolaier,  Rosenbach,  Fliigge,  and  Beumer  before 
him.  He  likewise  was  unable  to  obtain  a  pure  cultivation  by  suc- 
cessive generations,  as  even  the  last  growth  was  always  contami- 
nated by  a  bacillus  of  putrefaction.  Of  particular  importance  is 
the  observation  made  by  him,  that  the  secretions  from  the  wounds 
and  the  exudation  from  the  part  the  seat  of  tetanic  convulsions, 
when  dried  and  preserved  between  two  sterilized  watch-glasses 
retained  their  virulent  properties  for  at  least  four  months.  All 
animals  inoculated  with  dust  from  the  debris  in  the  interior  of  the 
church  were  attacked  with  tetanus.  Control  experiments  with  dust 
from  the  ruins  at  Diauo- Marina  never  proved  successful.  Of  the 
many  persens  injured  during  the  same  earthquake  at  this  place,  not 
one  was  attacked  by  tetanus. 

Beumer  ("  Zur  Aetiologie  des  Trismus  sive  Tetanus  neonatorum," 
Zeitschrift  fur  Hygiene,  B.  iii.  S.  242)  found  Nicolaier's  bacillus  in 
a  case  of  tetanus  neonatorum.  He  made  numerous  efforts  to  obtain 
a  pure  culture  by  successive  cultivations,  but  failed,  as  others  had 
before  him.  He  found  the  growth  contaminated  by  cocci  and  a 


PTOMAINES    OF    THE    BACILLUS    TETANI.  151 

smaller  bacillus.  He  also  made  numerous  inoculation  experiments 
with  different  kinds  of  earth.  Of  ten  experiments  with  soil  taken 
from  the  ocean  beach,  tetanus  followed  in  only  two.  On  the  other 
hand,  of  ten  inoculations  with  garden  earth  and  street  dust,  all  proved 
successful  but  one.  Of  three  cases  of  tetanus  which  recently  came 
under  the  observation  of  Lumniczer  ("  Beitrage  zur  Aetiologie  des 
Tetanus,"  Wiener  med.  Presse,  B.  xxx.  Nos.  10-12)  he  was  able  to 
demonstrate  the  microorganism  in  one.  In  this  case  the  attack 
followed  a  gunshot  injury.  After  the  disease  had  developed  frag- 
ments of  hemp  were  removed  from  the  canal  made  by  the  bullet, 
and  in  them  the  characteristic  bacillus  was  found  Cultures  were 
made  to  the  tenth  generation,  and  with  them  animals  were  inocu- 
lated and  tetanus  was  invariably  produced.  Pus  taken  from  ab- 
scesses produced  at  that  point  of  inoculation  contained  the  bacillus, 
and  injection  experiments  made  with  it  yielded  positive  results. 
Cultures  made  from  the  blood  or  organs  of  the  tetanic  animals  re- 
mained sterile.  Inoculation  with  blood  from  these  animals  proved 
harmless.  Kitasato  (op.  cit.)  experimented  with  a  pure  culture  of 
the  bacillus  of  tetanus  on  mice,  rats,  guinea-pigs,  and  rabbits,  and 
never  failed  in  producing  the  disease,  provided  a  sufficiently  large 
dose  of  the  culture  was  administered.  Jn  mice  the  disease  appeared, 
without  exception,  24  hours  after  the  inoculation,  and  proved  fatal 
in  2  or  3  days.  The  tetanic  convulsions  were  first  always  local, 
appearing  at  the  point  of  inoculation,  becoming  gradually  more 
diffuse.  He  was  unable  to  find  bacilli  at  the  seat  of  inoculation, 
in  the  blood  or  any  of  the  organs  of  the  body.  He  believes  that  if 
the  tetanus  is  produced  by  inoculation  with  a  pure  culture  the 
bacilli  do  not  remain  in  the  body  for  any  length  of  time,  but  are 
rapidly  eliminated.  The  same  question  has  been  raised  in  connec- 
tion with  the  pathogenic  action  of  the  bacillus  of  tetanus  as  with 
the  pus-microbes,  Is  the  disease  of  which  it  is  the  specific  cause  due 
to  the  presence  of  the  microbe,  or  its  products  in  the  organism  (the 
ptomaines)  ?  Brieger,  by  his  indefatigable  labors,  has  demonstrated 
beyond  all  doubt  that 

1  he  Ptomaines  of  the  Bacillus  Tetani  cause  Tetanic  Convulsions. 

Brieger  ("Zur  Kenntnissder  Aetiologie  des  Wundstarrkrampfes 
nebst  Bemerkungen  iiber  das  Cholera- roth,"  Deutsche  med.  Wochen- 
schrift,  1887,  p.  303)  has  succeeded  in  isolating  four  toxic  sub- 
stances from  mixed  cultivations  of  tetanus  bacilli  in  sterilized  meat 
emulsions.  The  first,  tetauiu,  in  doses  of  a  few  milligrammes  ad- 
ministered subcutaneously  in  mice  produced  the  characteristic  symp- 
toms of  tetanus.  The  second,  tetanotoxin,  causes  first,  tremors, 
later,  paralysis  and  convulsions.  The  third,  muriate  of  toxin,  has 


152  TETANUS. 

not  been  designated  by  a  special  name  by  Brieger,  it  produces  also 
well-marked  symptoms  of  tetanus,  but  besides  excites  the  salivary 
and  lachrymal  glands  to  increased  functional  activity.  The  last, 
spasmotoxin,  produces  severe  clonic  and  tonic  spasms  which  pros- 
trate the  animal  at  once.  Besides  meat  emulsion,  the  contused 
brain  substance  from  horses  and  cattle  was  used,  also  cow's  milk 
mixed  with  carbonate  of  lime.  It  seemed  that  the  culture  substance 
determined  to  a  certain  extent  the  kind  of  toxin  which  was  pro- 
duced ;  thus  in  cultures  grown  in  brain  substance  besides  tetanin, 
tetano-toxin  was  found  in  greatest  quantity;  old  cultures,  in  which 
the  tetanus  bacilli  were  dead,  produced  none  of  these  toxic  agents. 

The  same  author  ("  Ueber  des  Yorkommen  von  Tetaniu  bei  einem 
an  Wuudstarrkrampf  erkraukteu  Individ  uum,"  JBerl.  Min.  Wocken- 
schrift,  April  23,  1888)  has  very  recently  been  successful  in  isolating 
tetaniu  from  the  amputated  arm  of  a  patient  the  subject  of  tetanus. 
Tetanus  had  developed  a  few  days  after  a  severe  crushing  injury  of 
the  hand  and  forearm.  The  first  symptoms  manifested  themselves 
in  the  morning,  and  at  twelve  o'clock  (noon)  the  operation  was 
performed ;  at  five  o'clock,  on  the  same  day,  the  patient  expired 
suddenly  during  one  of  the  tetanic  convulsions.  The  bacilli  of 
tetanus  were  found  in  the  serum  taken  from  the  oedematous  portion 
of  the  forearm  in  connection  with  other  bacilli  of  different  length, 
staphylococci  and  streptococci.  Serum  containing  these  microbes 
when  injected  under  the  skin  of  mice,  guinea-pigs,  and  rabbits  in- 
variably produced  tetanus ;  on  the  other  hand,  a  dog  treated  in  the 
same  manner,  as  well  as  after  injections  of  tetaniu,  remained  well. 
A  horse  inoculated  with  a  culture  of  bacilli  in  meat  emulsion  showed 
no  symptoms  of  tetanus,  but  an  abscess  formed  at  the  point  of 
inoculation.  The  infiltrated  tissues  of  the  amputated  forearm  planted 
on  sterilized  meat  emulsion,  solid  blood-serum,  and  emulsion  made 
of  the  flesh  of  fish,  yielded,  besides  ammonia,  only  tetaniu ;  no  trace 
of  tetano-toxin,  spasmo-toxin,  nor  the  unnamed  toxin  which  could 
be  obtained  from  Rosenbach's  bacillus.  A  moderate  dose  of  tetanin 
injected  into  the  subcutaneous  tissue  of  a  horse  produced  muscular 
contractions  which  lasted  for  a  considerable  length  of  time,  but  the 
characteristic  symptoms  of  tetanus,  as  it  is  seen  in  horses,  did  not 
appear. 

The  clinical  and  experimental  researches  quoted  above  demon- 
strate that  the  same  bacillus  is  found  in  the  wound  secretions,  the 
tissues,  and,  in  some  instances,  in  the  blood  of  tetanic  patients,  and 
that  tetanus  in  animals  can  be  produced  by  injection  of  wound 
secretions  of  tetanic  patients,  or  by  using  cultivations — facts  which 
have  sufficiently  established  the  microbic  nature  of  the  disease.  The 
stage  of  incubation,  both  in  man  and  animals,  appears  to  be  extremely 
variable ;  in  some  instances  lasting  only  twenty-four  hours,  while 


PTOMAINES    OF    THE    BACILLUS    TETANI.  153 

in  others  weeks  may  lapse  between  the  time  of  inoculation  and  the 
first  manifestations  of  the  disease.  This  may  depend  on  one  of 
three  things:  1.  The  number  of  bacilli  introduced  may  be  so  small 
that  a  much  longer  time  is  necessary  before  active  symptoms  are 
produced  than  if  a  larger  quantity  had  been  introduced,  as  Watson 
Cheyne  has  shown  that  in  animals  the  injection  of  a  limited  num- 
ber of  the  bacilli  of  tetanus  produced  no  symptoms.  2.  The  loca- 
tion of  the  infection-atrium  and  anatomical  characteristics  of  the 
tissues  surrounding  it  may  influence  the  time  which  is  necessary  to 
develop  the  disease.  3.  Brieger's  investigations  have  shown  that 
tetanic  convulsions  in  animals  are  produced  by  injections  of  tetauin, 
one  of  the  toxic  ptomaines  derived  from  cultivations  of  the  bacillus 
of  tetanus,  and  it  is  more  than  probable  that  the  active  symptoms 
of  tetanus  in  man  are  due  not  to  the  presence  in  the  tissues  of  the 
bacillus,  but  to  the  toxic  action  of  the  ptomaines  on  the  spinal  cord, 
so  that  the  length  of  the  stage  of  incubation  is  further  modified  by 
the  capacity  of  the  infected  tissues  to  yield  the  different  ptomaines. 
The  degree  of  virulence  of  the  bacillus  of  tetanus  must  certainly 
play  an  important  part  not  only  in  determining  the  length  of  the 
incubation  stage,  but  also  the  intensity  of  symptoms.  There  can 
be  no  doubt  that  both  the  acute  and  chronic  forms  of  tetanus  are 
caused  by  the  same  microbe,  and  that  the  clinical  difference  depends 
upon  the  degree  of  virulence  of  the  primary  cause.  Whether  culti- 
vations from  chronic  cases  of  tetanus  can  produce  an  acute  and 
rapidly  fatal  attack  in  animals  remains  to  be  determined.  In  this 
direction  I  have  recently  made  an  observation  which,  if  not  con- 
vincing, is,  at  least,  very  suggestive.  A  boy,  fifteen  years  of  age, 
previously  in  good  health,  was  attacked  with  acute  osteomye- 
litis in  the  lower  extremity  of  the  femur.  The  surgeon  in  attend- 
ance trephined  the  bone  over  its  outer  and  lower  aspect  during 
the  first  few  days  and  before  an  abscess  had  formed  in  the  soft 
parts.  A  few  days  after  the  operation  trismus  set  in,  followed  by 
typical  chronic  tetanus.  Six  weeks  later,  the  patient  entered  the 
Milwaukee  Hospital,  and  was  placed  under  my  charge.  At  this 
time  the  patient  had  become  emaciated  to  a  skeleton.  Trismus  and 
opisthotonus  were  well  marked,  and  the  lower  extremities  were 
rigid  and  fixed  in  the  extended  position.  The  slightest  touch,  or  a 
draught  of  air  in  the  room,  would  bring  on  intense  convulsive 
attacks  lasting  for  several  minutes,  attended  by  excruciating  pain. 
Profuse  fetid  discharge  at  the  site  of  operation;  pulse  140,  tempera- 
ture from  99°  to  101°  F.  (37.3°  to  38.3°  C.).  Believing  that  the 
primary  infection  had  taken  place  through  the  operation  wound, 
and  that  osteomyelitic  products  served  the  purpose  of  a  nutrient 
medium  for  the  bacillus  tetani,  I  determined  to  operate  in  spite  of 
the  grave  symptoms.  As  the  spinal  cord  at  this  stage  of  the  dis- 


154  TETANUS. 

ease  was  necessarily  the  seat  of  intense  congestion,  I  resorted  to 
chloroform  as  an  anaesthetic  instead  of  ether.  The  usual  operation 
for  necrosis  of  the  lower  end  of  the  femur  was  performed,  and  a 
large  triangular  sequestrum  removed  from  the  lower  and  posterior 
aspect  of  the  bone.  The  involucrum  was  imperfect  and  its  inner 
side  lined  with  a  thick  layer  of  flabby  granulations.  Gelatin  tubes 
were  inoculated  with  blood,  pus,  and  granulation  tissue.  The  blood 
cultivations  remained  sterile,  while  the  two  remaining  tubes  showed 
a  copious  growth  of  staphylococcus  pyogenes  albus  which  rapidly 
liquefied  the  gelatin.  A  portion  of  the  granulation  tissue  was  dis- 
infected with  a  weak  solution  of  carbolic  acid,  dried  between  layers 
of  antiseptic  gauze,  and  inserted  under  the  skin  of  a  rabbit.  No 
suppuration  followed,  and  the  animal  remained  perfectly  well  for 
six  weeks,  when  both  posterior  extremities  became  rigid  so  that  it 
could  only  move  from  place  to  place  by  dragging  the  hind  legs. 
The  next  day  tetanic  convulsions  affecting  the  muscles  of  the  back 
and  all  the  limbs  appeared,  and  on  the  fourth  day  death  supervened. 
The  interesting  features  in  this  case  are  that  the  patient  recovered 
from  the  tetanus  after  a  long  illness,  extending  over  three  months ; 
that  marked  improvement  followed  the  operation,  which  had  for  its 
object  thorough  disinfection  of  the  infection-atrium  ;  and  that  the 
inoculation  with  granulation  tissue  in  the  rabbit  was  followed  by 
an  acute  attack  of  tetanus  six  weeks  after  infection.  In  the  experi- 
ments related  above  the  animals  were  inoculated  with  cultivations, 
or  with  wound  secretions  from  tetanic  patients ;  the  stage  of  incu- 
bation rarely  extended  over  two  to  three  days,  and  often  only 
eighteen  to  twenty-four  hours,  aud  the  disease  produced  death  in 
from  twelve  hours  to  three  days. 

Prophylactic  and  Curative  Treatment  of  Tetanus  by  Antiseptic 

Agents. 

More  than  a  year  ago  Sormani  (La  Riforma  Medica  di  Napoli, 
January  11-13,  1890),  of  Naples,  found  that  iodofortn  was  one  ol 
the  most  energetic  disinfectants  of  the  virus  of  tetanus,  and  that 
iodol  and  an  acid  (2  per  cent.)  solution  of  corrosive  sublimate  were 
similar  in  their  action.  A  second  series  of  experiments  has  shown 
that  also  chloral  and  chloroform  had  a  similar  power.  Since  then 
Mazzuschelli  has  used  iodoform  (locally)  in  two  cases,  which  in  and 
toward  the  end  of  May,  1889,  came  under  treatment.  In  one  case 
a  girl  while  working  in  a  garden  with  a  spade,  inflicted  upon  her- 
self a  large,  torn  wound  in  the  calf  of  the  right  leg.  Eight  days 
after  tetanus  set  in  and  she  was  taken  into  the  hospital  at  Pa  via. 
After  removal  of  the  dead  tissue  the  wound  was  cleansed  with  a  2 
per  cent,  solution  of  sublimate,  dusted  over  with  iodoform,  and 


PKOPHYLACTIC  AND  CURATIVE  TREATMENT.   155 

chloral  hydrate  given  internally.  The  patient  died  twelve  hours 
later.  In  the  other  case,  the  patient  had  run  a  splinter  into  her 
foot  between  the  great  and  second  toe  while  following  a  path  bare- 
footed over  a  field.  Six  days  later  tetanus  made  its  appearance, 
the  splinter  was  removed,  and  the  wound  treated  as  in  the  preced- 
ing case;  death  four  days  later,  ten  days  after  the  injury. 

In  the  first  case  Sormani  inoculated  two  rats  and  one  rabbit  with 
the  tissue  which  was  removed  from  the  wound  before  dusting  with 
iodoform.  All  these  animals  died  from  tetanus  from  forty-eight  to 
ninety-six  hours  after  inoculation.  Two  rabbits  inoculated  with  a 
fragment  of  tissue  from  the  wound  after  the  death  of  the  patient 
remained  alive. 

In  the  second  case  a  piece  of  the  iodoformized  tissue  and  one 
from  the  tissues  lying  more  deeply  were  used  for  inoculation  of  two 
rats,  which,  however,  did  not  contract  the  disease.  A  culture-glass 
filled  with  agar  inoculated  with  a  fragment  of  the  wound-tissues 
after  the  disinfection  remained  sterile;  another  tube  inoculated  with 
tissue  removed  more  deeply  developed  staphylococci. 

The  author  concludes,  from  these  and  further  experiments,  that 
where  tetanus  is  already  developed  iodoform  is  not  able  to  prevent 
its  further  course,  but  may  neutralize  the  virus  on  the  surface  of 
the  wound. 

Baccelli  (Riforma  Medica,  January  25,  1890)  used  subcutaneous 
injections  of  carbolic  acid  in  doses  of  1  centigramme  every  hour. 
In  1887  he  cured  a  grave  case,  and  now  he  has  another  such  a  one 
under  treatment,  where  the  injections  have  produced  such  an  im- 
provement that  recovery  is  assured. 


CHAPTER    XVI. 

TUBERCULOSIS. 

OF  all  the  microbic  diseases,  tuberculosis  is  of  the  greatest 
interest  and  importance  to  the  surgeon.  Of  the  greatest  interest 
because  the  tubercular  lesions  which  come  under  his  care  are  more 
clearly  understood  from  a  scientific  standpoint  than  most  of  the 
other  surgical  diseases,  and  of  the  greatest  importance  on  account 
of  their  great  frequency.  That  large  class  of  diseases  which  were 
grouped  under  that  indefinite  and  vague  term,  scrofula,  in  the  text- 
books of  but  a  few  years  ago,  have  been  shown  by  recent  research 
to  be  identical  with  tuberculosis  etiologically,  clinically,  and  ana- 
tomically. It  is  the  object  of  this  part  of  the  book  to  give  a  brief 
description  from  a  bacteriological  and  clinical  standpoint  of  such 
localized  tubercular  lesions  which  by  general  consent  are  regarded 
as  surgical  affections  and  requiring  surgical  treatment. 

HISTORY. — The  results  obtained  from  the  crude  inoculation 
experiments,  which  were  made  by  Villemin,  pointed  strongly 
toward  the  infectiousness  of  tuberculosis,  and  since  that  time  dili- 
gent search  was  made  to  discover  and  isolate  a  specific  micro- 
organism which  should  be  characteristic  of  this  disease.  Theories 
were  advanced,  microbes  were  found  and  described  which  were 
supposed  to  bear  a  direct  etiological  relationship  to  tuberculosis, 
but  nothing  definite  was  known  on  the  subject  until  Robert  Koch 
("  Die  Aetiologie  der  Tuberkulose,"  Berl.  kiln.  Wochenschrift, 
1882,  No.  15),  in  1882,  announced  to  the  profession  his  great  dis- 
covery. He  had  found  and  demonstrated  the  true  cause  of  tuber- 
culosis, the  bacillus  of  tuberculosis,  and  in  his  first  publication 
brought  such  convincing  proof  of  the  correctness  of  his  claim,  that, 
with  few  exceptions,  it  brought  conviction  even  to  the  most  scepti- 
cal. He  had  not  only  found  the  bacillus,  but  showed  that  it  was 
constantly  present  in  all  tubercular  lesions.  He  had  isolated  and 
cultivated  the  bacillus  from  tubercular  tissue  ;  and,  finally,  he  had 
furnished  the  crucial  test — had  produced  artificial  tuberculosis  in 
animals  by  inoculation  which  was  identical  with  tuberculosis  in 
man.  A  number  of  pathologists,  who  inoculated  animals  with 
non-tubercular  material,  claimed  that  they  had  produced  pathologi- 
cal conditions  analogous  to  those  found  in  animals  which  had  been 
infected  with  the  virus  of  tuberculosis.  Further  experimenta- 


DESCRIPTION    OF    THE     BACILLUS    TUBERCULOSIS.       157 

tion  soon  showed  that  these  were  instances  of  pseudo-tuberculosis  ; 
that  while  the  gross  appearances  of  the  lesions  resembled  true 
tuberculosis,  inoculations  with  this  material  never  reproduced  the 
disease,  while  inoculations  with  tubercular  material  could  be  done 
through  a  series  of  animals  without  impairing  the  potency  of  the 
virus,  or  varying  the  constancy  of  the  results.  Koch's  discovery 
did  not  lead  to  such  energetic  search  for  the  bacillus  of  tuberculosis 
among  surgeons  as  physicians,  because,  as  Konig  asserts,  the  symp- 
toms and  signs  of  the  tubercular  affections  coming  under  the  obser- 
vation of  surgeons  are  so  characteristic,  that  for  practical  purposes 
a  correct  diagnosis  could  be  made  in  the  majority  of  cases  without  a 
knowledge  of  their  microbic  nature  and  the  improved  methods  for 
making  a  positive  diagnosis  derived  therefrom.  Koch,  himself,  in 
the  publication  above  referred  to,  demonstrated  the  presence  of  the 
bacillus  in  lupus,  scrofulous  glands,  tubercular  joints,  etc.  He 
called  attention  to  the  fact  that  in  these  affections  the  bacillus  can 
be  constantly  found  in  giant  cells  and  between  the  epithelioid  cells, 
while  it  is  more  difficult  to  find  it  in  cheesy  products,  unless  casea- 
tion  has  taken  place  quite  rapidly. 

Weichselbaum  ("Tuberkelbacillen  im  Blut.,"  etc.,  Wiener  meet. 
Wochenschrifi,  1884,  Nos.  12,  13),  Meisels,  and  Lustig  found 
tubercle  bacilli  in  the  blood  in  cases  of  acute  miliary  tuberculosis, 
both  during  life  and  after  death.  Schuchardt  and  Krause  ("  Ueber 
das  Yorkommen  der  Tuberkelbacillen  bei  fuugosen  uud  scrofu- 
losen  Entziindungen,"  Fortschritte  der  Medicin,  B.  i.  S.  277) 
examined  forty  cases  of  tuberculosis  of  bones,  joints,  tendon- 
sheaths,  and  the  skin  in  Volkmanu's  klinik,  and  never  failed  in 
finding  bacilli,  although  in  some  specimens  careful  and  prolonged 
search  had  to  be  made.  They  found  the  bacilli  in  various  lesions 
which  had  formerly  been  regarded  as  scrofulous  affections. 

Schlegtendal  ("  Ueber  das  Vorkommen  der  Tuberkelbacillen  im 
Eiter,"  Fortschritte  d.  Medicin,  B.  i.  S.  537)  examined  520  speci- 
mens of  pus  from  tuberculous  suppurations  and  found  bacilli  pre- 
sent in  about  75  per  cent,  of  the  cases.  Mogliug  (Die  Chirur- 
gischen  Tuberkulosen,  Tubingen,  1884)  found  the  bacilli  never  absent 
in  tubercular  pus  from  53  patients. 

During  the  last  few  years,  surgeons  have  made  valuable  contri- 
butions to  surgical  literature  on  the  subject  of  tuberculosis  corrobo- 
rative of  the  statements  of  Koch,  which  have  placed  many  hereto- 
fore obscure  lesions  within  the  range  of  rational  and  successful 
surgical  treatment. 

DESCRIPTION  OF  THE  BACILLUS  TUBERCULOSIS. — The  bacillus 
described  by  Koch  as  the  essential  cause  of  all  forms  of  tubercular 
inflammation  appears  in  the  shape  of  very  thin  rods  from  two  to 
eight  micromillimetres  in  length,  and  rounded  at  the  ends.  They 


158  TUBERCULOSIS. 

are  straight  or  curved,  and  frequently  beaded,  occur  singly,  in  pairs 
or  in  bundles.  In  the  tissues  they  are  found  in  the  interior  of 
giant  cells  and  within  and  between  epithelioid  cells.  The  bacillli 
of  tuberculosis  are  non-motile  and  consequently  possess  no  power  of 
locomotion  and  cannot  penetrate  into  the  tissues  without  assistance. 
Spore-formation  occurs,  even  within  the  animal  body,  the  spores 
having  the  appearance  of  clear  vacuoles. 

METHODS  OF  STAINING. — For  section-staining  Ehrlich's  method 
is  the  best : 

Saturated  alcoholic  solution  of  methyl-violet  or  fuchsin      11  parts. 

Aniline  water 100      " 

Absolute  alcohol    ....        .         .         .  10      " 

Sections  are  left  for  twelve  hours  in  this  solution.  Treat  the 
specimen  with  1  :  3  solution  of  nitric  acid  a  few  seconds.  Wash 
in  alcohol  (60  per  cent.)  for  a  few  minutes;  after-stain  with  diluted 
solution  of  vesuvin  or  methyleue-blue  for  a  few  minutes ;  wash 
again  in  60  per  cent,  alcohol,  dehydrate  in  absolute  alcohol,  clear 
with  cedar  oil,  mount  in  Canada  balsam.  The  examination  of 
fluids  can  be  done  rapidly  and  most  satisfactorily  by  Gibbes7 
method. 

Gibbes7  magenta  solution  : 

Magenta 2  parts. 

Aniline  oil 3      " 

Alcohol  (specific  gravity  0.830) 20      " 

Distilled  water 20      " 

Stain  cover-glass  preparations  in  this  solution  for  fifteen  or 
twenty  minutes  ;  wash  in  (1  :  3)  solution  of  nitric  acid  until  the 
color  is  removed ;  rinse  in  distilled  water.  After-stain  with 
methyleue-blue,  methyl-green,  iodine-green,  or  a  watery  solution  of 
crysoidin,  five  minutes ;  wash  in  distilled  water  until  no  more  color 
comes  away.  Transfer  to  absolute  alcohol  for  five  minutes,  dry, 
and  preserve  in  Canada  balsam. 

CULTIVATION  EXPERIMENTS.— -The  best  culture  medium  is 
solid  sterilized  blood-serum  of  the  cow  or  sheep,  with  or  without 
the  addition  of  gelatin  at  a  temperature  of  37°  to  38°  C.  (98.6°  to 
100.4°  F.).  The  bacillus  grows  very  slowly  and  only  between  the 
temperatures  of  30°  and  41°  C.  (86°  and  *105.8°  F.).  In  about 
a  week  or  ten  days,  the  culture  appears  as  little  whitish  or  yellowish 
scales  and  grains.  The  bacillus  can  also  be  cultivated  in  a  glass 
capsule  on  blood-serum,  and  the  appearance  of  the  growth  studied 
under  the  microscope.  The  scales,  or  pellicles,  are  then  seen  to  be 
made  up  of  colonies  of  a  perfectly  characteristic  appearance.  The 
growth  ceases  after  three  or  four  weeks.  The  blood-serum  is  not  • 
liquefied,  unless  putrefactive  bacteria  contaminate  the  culture. 


PLATE    V. 


Tubercle  bacilli  containing  spores.     (R.  Koch.)     Zeiss  ^.    O.  4. 


PLATE    VI. 


Tubercle  bacilli  from  a  tubercular  cavity.     Carbol-fuchsin, 
nitric  acid,  methyl-blue.     Zeiss  y1^.     O.  4 


INOCULATION    EXPERIMENTS.  159 

Nocard  et  Roux  ("  Sur  la  culture  du  bacille  de  la  Tuberculose," 
Annales  de  V Institute  Pasteur,  i.  1887,  No.  1,  pp.  19-29)  have 
found  that  coagulated  blood -serum  is  improved  for  the  growth  of 
the  bacillus  of  tuberculosis  by  adding  peptone,  soda,  and  sugar. 
A  further  addition  of  6  to  8  per  cent,  of  glycerin  favors  the 
growth  of  the  bacillus  still  more,  while  at  the  same  time  it  prevents 
the  formation  of  a  crust  upon  the  culture  medium,  which  otherwise 
forms  by  evaporation.  They  also  made  successful  cultivations 
upon  agar-agar  bouillon,  to  which  was  added  6  to  8  per  cent,  of 
glycerin,  kept  at  a  temperature  of  39°  C.  (102.2°  F.). 

INOCULATION  EXPERIMENTS — Even  before  the  discovery  of  the 
bacillus  of  tuberculosis  by  Koch,  genuine  tuberculosis  was  produced 
in  animals  by  inoculation  with  the  products  of  what  was  then 
described  as  scrofula.  Hueter  inoculated  the  anterior  chamber  of 
the  eye  in  rabbits  with  lupus  tissue  and  produced  tuberculosis  of 
the  iris.  Schiiller  (  Untersuchung  uber  die  Entstehung  und  Ursache 
der  scrofidosen  und  tuberculosen  Getenldeiden,  1880)  introduced 
fragments  of  lupus  tissue  into  the  veins  of  animals,  and  in  this 
way  produced  pulmonary  tuberculosis.  He  also  claimed  to  have 
discovered  the  microbe  of  tuberculosis  by  fractional  cultivation  from 
lupus  tissue  which,  when  conveyed  into  the  vessels  of  the  lungs, 
produced  phthisis,  and  when  injected  into  joints  tubercular  inflam- 
mation, caseation,  and,  finally,  miliary  tuberculosis.  Koch  (Mit- 
theilungen  aus  dem  Kaiserlichen  Gesundheitsamte,  B.  xi.  1883) 
inoculated  the  anterior  chamber  of  the  eyes  of  eighteen  rabbits 
from  five  cases  of  lupus,  and  in  all  of  them  tuberculosis  of  the  iris 
was  produced,  and,  if  life  was  prolonged  for  a  sufficient  length  of 
time,  was  followed  by  tuberculosis  of  the  lymphatic  glands  of  the 
neck,  lungs,  kidneys,  liver,  and  spleen.  Similar  results  were 
obtained  in  five  guinea-pigs. 

Cornet  has  recently  made  numerous  experiments  in  Koch's 
laboratory  on  animals  to  ascertain  the  inoctilability  of  tuberculosis 
through  abrasions  of  the  skin,  He  found  that  if  lupus  tissue,  or 
a  pure  culture  of  tubercle  bacilli,  is  applied  to  a  cutaneous  abrasion, 
the  result  in  most,  if  not  in  all,  cases  is  a  local  tuberculosis  in  the 
adjacent  lymphatic  glands,  and,  later,  a  general  miliary  tuberculosis. 

The  same  author  ("  Demonstration  von  tuberculosen  Driisen- 
Schwellungen  nach  Impfuugen  von  Tuberkel  bacillen  bei  Hunden," 
Centralblatt  f.  d.  Gesammte  Medicin,  No.  29,  1889)  made  subse- 
quently a  long  series  of  experiments  on  dogs  to  ascertain  the  differ- 
ent avenues  through  which  infection  is  known  to  take  place. 
Tuberculous  sputum  and  pure  cultures  inserted  into  the  lower 
conjunctival  sac  in  healthy  dogs  produced  tissue  hyperplasia  at  the 
seat  of  inoculation  and  was  followed  by  infection  of  the  cervical 
glands  on  the  corresponding  side.  Some  of  the  glands  had  under- 


160  TUBERCULOSIS. 

gone  caseation,  and  the  presence  of  bacilli  could  be  demonstrated 
in  all  of  the  pathological  products.  In  other  animals  the  tubercu- 
lous material  was  introduced  into  the  nasal  cavity.  The  cervical 
glands,  especially  those  on  the  corresponding  side,  became  enlarged 
and  caseated.  Infection  through  the  mouth  by  depositing  the 
tuberculous  material  in  a  depression  made  with  a  blunt  instrument 
between  the  canine  teeth  resulted  also  in  tuberculosis  of  the  cervical 
glands.  Infection  of  the  external  meatus  of  the  ear  without  creat- 
ing intentionally  an  infection-atrium  was  followed  by  infection  of 
the  lymphatic  glands  behind  the  ear  and  along  the  neck  on  the 
same  side.  Cutaneous  tuberculosis  in  the  form  of  an  ulcerating 
lupus  was  produced  by  shaving  the  skin  on  one  side  of  the  nose 
and  face,  and  scratching  it  with  a  finger-nail  infected  with  tubercu- 
lous material.  Injection  of  the  material  into  the  healthy  vagina 
of  bitches  resulted  in  local  tuberculosis  and  secondary  infection  of 
the  inguinal  glands.  Inoculations  of  other  parts  were  followed  by 
the  same  train  of  symptoms — local  tuberculosis  at  the  seat  of  infec- 
tion followed  by  extension  of  the  tuberculous  process  along  the 
nearest  lymphatic  channels,  The  lungs  were  found  affected  only 
in  two  of  the  animals. 

Cornil  and  Leloir  implanted  lupus  tissue  into  the  peritoneal 
cavity  of  guinea-pigs,  and  in  five  cases,  out  of  fourteen  experiments, 
produced  peritoneal  and  general  tuberculosis.  Implantations  from 
these  animals  into  healthy  animals  again  yielded  positive  results. 

Pagenstecher  and  Pfeiifer  (Berliner  kiin.  Wochenschrift,  1883) 
took  the  secretion  of  the  conjunctiva  from  patients  suffering  from 
lupus  of  this  structure  and  injected  it  into  the  anterior  chamber  of 
the  eye  in  rabbits.  After  five  to  six  weeks,  nodules  could  be  seen 
on  the  surface  of  the  iris  which  were  in  every  respect  identical  with 
tuberculosis  of  this  organ.  Doutrelepont  ("  Die  Aetiologie  des 
Lupus  vulgaris,"  Proceedings  of  International  Congress,  Copen- 
hagen) inoculated  the  peritoneal  cavity  of  fifty  guinea-pigs,  and  in 
eight  rabbits  the  anterior  chamber  of  the  eye,  and  in  all  of  the  ani- 
mals local  tuberculosis  was  produced  at  the  point  of  inoculation ;  and 
in  three  of  the  guinea-pigs,  and  in  one  rabbit,  the  local  disease  was 
followed  by  general  tuberculosis.  The  advances  in  our  knowledge 
of  the  etiology  of  tuberculosis,  the  discovery  of  the  bacillus,  and 
the  production  in  animals  of  tuberculosis  by  implantation  of  lupus 
tissue  have  finally  settled  the  identity  of  tuberculosis  and  lupus. 
As  tuberculosis  is  now  diagnosed  wherever  the  respective  bacillus 
is  found,  another  diagnostic  significance  is  admitted  even  by  those 
who  are  inclined  to  be  sceptical  in  regard  to  the  etiological  role 
played  by  it.  Koch  produced  artificial  tuberculosis  in  over  five 
hundred  animals  with  material  from  different  tubercular  lesions  and 
examined  them  all  with  the  greatest  care.  Of  the  bacillus  he  pro- 


PLATE    VII. 


Beg.T. 


&. 


*  m  y>  *•'*&  ^^  r 

tif  y^fff* 


Of. 


Tubercular  eruption  in  the  iris  of  a  rabbit,  fifth  day  after  inoculation. 
Zeiss  TV  (Baumgarten.) 

Beg.  T.  Formation  of  tubercles  beginning  (separation  of  white 
corpuscles.). 

E.  Endothelium  of  the  anterior  surface  of  the  iris. 

Ep.  Epithelium  of  the  posterior  surface  of  the  iris. 

P.  Iris  parenchyma. 

Gf.   Bloodvessels. 


INOCULATION    EXPEKIMENTS.  161 

duced  forty-three  pure  cultures,  some  of  which  he  continued  through 
over  thirty  generations,  occupying  a  period  of  two  years.  We  shall 
see  that  inoculations  with  material  from  so-called  scrofulous  glands 
produce  the  same  effect  as  when  lupus  tissue  is  used,  and  must, 
therefore,  attribute  their  existence  to  the  same  cause. 

Arloing  (Comptes  rendus,  t.  xcix.  p.  661)  prepared  an  emulsion 
from  a  simple  scrofulous  gland,  caseous  in  the  centre,  which  was 
taken  from  a  boy  aged  fourteen.  This  was  injected  beneath  the 
skin  of  ten  rabbits  and  the  same  number  of  guinea-pigs.  Visceral 
tuberculosis  developed  in  all  guinea-pigs,  but  the  rabbits  remained 
healthy,  except  that  two  showed  yellow  caseous  granulations  at  the 
seat  of  inoculation.  From  a  gland  removed  later,  from  the  same 
boy,  a  similar  emulsion  was  made  and  injected  into  the  peritoneal 
cavity  of  six  rabbits  and  six  guinea-pigs.  As  before,  the  guinea- 
pigs  all  presented  tubercular  lesions ;  the  rabbits,  on  being  killed, 
were  found  to  be  perfectly  healthy.  In  two  instances,  pus  from 
strumous  abscesses  gave  similar  results.  Some  glands  excised  from 
the  neck  of  a  young  woman  produced  tuberculosis  both  in  rabbits 
and  in  guinea-pigs,  but  the  patient  died  three  weeks  after  the  opera- 
tion from  miliary  tuberculosis.  Arloing  appears  to  consider  this 
case  as  outside  the  general  category  of  strumous  glands.  From 
these  experiments  he  inferred  that  either  scrofula  and  tuberculosis 
were  nearly  allied  affections,  but  caused  by  different  agents,  or  they 
were  derived  from  a  single  virus,  of  which  the  activity  was  modified 
in  the  scrofulous  form. 

Bollinger  (u  Ueber  den  Einflus  der  Verdiinnung  auf  die  Wirk- 
samkeit  des  tuberculosen  Giftes,"  Munch,  med.  Wochenschrift,  No. 
43,  1889)  has  studied  experimentally  the  effect  of  dilutions  of 
tuberculosis  material.  He  found  that  infectious  milk  from  a  tuber- 
culous cow  which  produced  typical  local  tuberculosis  by  iutra- 
peritoneal  injections,  if  diluted  from  1  :  40  to  1  :  100  has  lost  its 
virulence.  The  sputum  of  phthisical  patients  was  found  much 
more  virulent  and  had  not  lost  its  power  to  produce  tuberculosis  on 
being  diluted  1  :  100,000,  on  being  injected  into  the  abdominal 
cavity  or  the  subcutaneous  connective-tissue.  Feeding  experiments 
with  sputum  diluted  1  :  8  yielded  negative  results.  Pure  cultures 
remained  virulent  when  diluted  1  :  400,000.  All  the  experiments 
proved  that  the  more  concentrated  the  material  and  the  greater  the 
number  of  bacilli  the  more  rapid  and  intense  was  the  development 
of  the  lesion  caused  by  the  injection.  In  guinea-pigs  it  was  esti- 
mated that  about  820  bacilli  were  necessary  to  produce  fatal  tuber- 
culosis. Intra-peritoneal  injections  did  not  always  produce  peri- 
toneal tuberculosis,  and  when  this  was  absent  the  organs  affected 
were  the  lymphatic  glands,  spleen,  lungs,  liver,  kidneys,  and 
genital  organs  in  the  order  of  frequency  named,  showing  that 

11 


162  TUBEKCULOSIS. 

localization  does  not  always  take  place  at  the  point  of  primary 
infection. 

Mr.  Eve  ("  On  the  Relation  of  Scrofulous  Gland  Disease  to  other 
forms  of  Tuberculosis ;  an  Experimental  Inquiry,"  British  Medical 
Journal,  April  14,  1888)  conducted  some  experiments  for  the  same 
purpose,  using  small  fragments  of  the  glands  prepared  with  steril- 
ized instruments,  and  the  possibility  of  infection  of  the  animals 
with  true  tuberculosis  was  negatived  by  the  precautions  taken.  As 
regards  the  results  of  the  experiments  on  rabbits  with  glands  from 
five  different  subjects,  the  material  from  these  cases  produced  vis- 
ceral tuberculosis;  from  one  case,  cold  abscesses;  and  in  one 
instance,  in  which  a  rabbit  was  inoculated  in  the  anterior  chamber 
of  the  eye,  it  escaped  infection  altogether.  No  bacilli  could  be  dis- 
covered in  the  gland.  Three  rabbits  inoculated  with  the  infected 
organs  from  a  guinea-pig,  proved  to  be  the  most  acute  cases  of 
tuberculosis  that  the  author  has  been  able  to  induce  by  strumous 
gland  disease  in  rabbits,  the  tubercles  being  widely  disseminated. 
The  bacilli  in  the  visceral  tuberculosis  were  generally  uniformly 
stained  with  even  outlines,  but  in  a  strumous  abscess  in  a  rabbit 
which  had  existed  for  eight  months  they  were  nearly  all  "beaded" 
or  uniformly  stained,  and  often  collected  in  groups  not  unlike 
clumps  of  micrococci. 

Wm.  Mueller  ("  Experimentelle  Erzeugung  der  typischen 
Knochentuberculose,"  Centralblatt  f.  C/iirurgie,  1886,  p.  233)  pro- 
duced the  characteristic  form  of  tuberculosis  in  bone  experimentally 
by  the  injection  of  tuberculous  material  into  the  nutrient  artery. 
Konig  for  a  long  time  had  claimed  that  the  wedge-shaped  seques- 
trum so  constantly  found  in  tubercular  foci  in  the  articular  extremi- 
ties of  the  long  bones,  was  due  to  occlusion  of  a  small  artery  by  a 
tubercular  emboltis.  Miiller's  experiments  were  made  to  prove 
this  clinical  observation.  He  made  sixteen  experiments  on  rabbits, 
injecting  tuberculous  pus  into  the  femoral  artery,  some  in  a  periph- 
eral, some  in  a  central  direction,  without  any  positive  results.  In 
a  second  series  the  same  material  was  thrown  into  the  nutrient 
arteries  of  the  femur  and  tibia.  Of  ten  of  these  cases,  two  showed 
a  tuberculous  focus  in  the  medulla  of  the  diaphysis  of  the  tibia,  in 
another  case  miliary  tuberculosis  in  the  femur  and  tibia,  and  in  the 
latter  bone  a  small  caseous  spot  in  the  spongy  part,  which  contained 
numerous  bacilli.  The  animals  were  killed  eight  weeks  after  the 
injection  and  showed  no  evidences  of  organic  disease,  except  few 
tubercles  in  the  lungs.  Twenty  experiments  were  made  on  young 
goats,  five  on  sheep,  and  two  on  .dogs.  The  tuberculous  material 
was  injected  directly  into  the  nutrient  artery  of  the  tibia,  the  tibial 
artery  being  tied  above  and  below  this  vessel.  Primary  union  of 
the  wound  was  obtained  in  all  cases  except  on  one  dog. 


INOCULATION-TUBERCULOSIS.  163 

In  the  dogs  and  sheep,  all  experiments  yielded  negative  results. 
In  the  goats  bone  affections  were  produced  which  were  identical 
with  tubercular  bone  lesions  found  in  man.  Most  frequently  the 
disease  was  established  in  the  diaphysis — cheesy  masses  and  granu- 
lation tissue  showing  themselves  in  the  medulla  and  cortical  sub- 
stance, or  tuberculous  osteomyelitis  with,  or  without,  sequestration. 
Typical  lesions  were  also  found  in  the  ends  of  the  bones  with,  and 
without,  implication  of  the  adjacent  joints.  In  two  of  these  cases 
the  epiphysis  was  affected,  while  in  three  the  shaft  was  involved. 
The  following  experiment  furnishes  a  good  illustration  of  the  iden- 
tity of  the  bone  disease  produced  experimentally,  and  the  disease 
as  it  occurs  in  man.  Tuberculous  material  was  injected  into  the 
tibial  artery  of  a  goat  three  months  old.  Wound  healed  in  eight 
days.  Some  lameness  four  months  later,  gradually  increasing  dur- 
ing the  next  nine  months.  At  the  same  time  a  swelling  appeared  at 
the  knee-joint.  Tibia  painful  on  outer  side.  Animal  killed  thirteen 
months  after  the  injection.  There  was  found  a  typical  fungous 
disease  in  the  knee-joint  most  advanced  at  the  sides,  a  wedge-shaped 
sequestrum  in  one  of  the  tuberosities  of  the  tibia,  and  a  small 
granulation  mass  in  the  centre  of  the  head  of  the  tibia,  and  two 
similar  granulation  masses  in  the  lower  epiphysis  of  the  femur. 
With  the  exception  of  the  lymphatic  glands  of  the  knee  joint,  no 
other  organs  were  affected.  In  some  cases  pulmonary  tuberculosis 
developed,  twice  general  tuberculosis.  The  rest  of  the  animals 
were  killed  when  they  began  to  show  lameness — fourteen  days  to 
thirteen  months  after  the  inoculation.  The  tubercular  lesions  thus 
produced  were  examined  for  bacilli  and  these  were  never  found 
absent.  The  starting-point  in  every  instance  must  have  been  a 
tubercular  embolus  in  one  of  the  small  arterial  branches  in  the 
extremity  of  the  bone. 

The  opinion  that  tubercle  is  capable  of  inoculation  was  held  by 
many  ancient  writers,  and  Laennec  himself,  after  a  nick  from  a  saw 
while  making  a  necropsy  on  a  phthisical  subject,  thought  that  he 
witnessed  an  example  of  inoculation  in  a  small  tubercle  in  the  skin, 
but  twenty  years  afterward  this  great  physician  and  teacher  was  in 
good  health,  though  finally  he  died  of  phthisis. 

Inoculation-tuberculosis. 

Schmidt  (u  Uebertragbarkeit  der  Tuberkulose  durch  cutaue  Imp- 
fung,"  Milnchen.  drtzliches  Intelliyenzblatt,  1883,  Nos.  47  and  48) 
made  a  number  of  experiments  to  ascertain  the  effect  of  inoculations 
of  superficial  abrasions  of  the  skin  with  the  virus  of  tuberculosis. 
In  guinea-pigs  he  made  slight  cutaneous  abrasions  of  the  skin  to 
which  he  applied  tubercular  material,  and  covered  the  point  of 


164  TUBEKCULOSIS. 

inoculation  with  collodium.     All  of  his  experiments  failed  in  pro- 
ducing tuberculosis,  while  in  the  control  animals  in  which  the  infec- 
tious material  was  introduced  into  the  subcutaneous  tissue,  or  into 
the  peritoneal  cavity,  tuberculosis  developed  without  a  single  excep- 
tion.    He  believes  that  the  results  of  these  experiments  are  only 
corroborative  of  the  assertion  previously  made  by  Bollinger  and 
Koch  that  the  susceptibility  of  the  cutis  for  tubercular  infection  is 
slight.     A  sufficient  number  of  well-authenticated  cases,  however, 
have  been  reported  during  the  last  few  years  to  prove  that  in  man 
tuberculosis  is  not  infrequently  contracted  by  the  absorption  of 
tubercular  material  through  small  wounds  and  superficial  abrasions 
of  the  skin.    Volkmann  a  number  of  years  ago  made  the  statement 
that  tubercular  infection  never  takes  place  through  large  operation 
wounds,  or  at  the  site  of  severe  injuries,  but  that  localization  of 
the  bacillus  is  likely  to  take  place  in  parts  the  seat  of  very  slight 
contusions,  or  what  may  appear  at  the  time  as  an  insignificant 
injury.     He  explained   this  by  assuming  that  the  active  tissue- 
changes  which  take  place  during  the  process  of  regeneration  after 
a  severe  trauma  prevented  the  infection.     In  studying  the  cases  of 
inoculation-tuberculosis,  which  will  be  referred  to  below,  it  will  be 
seen  that  the  infection-atrium  was  always  caused  by  a  trivial  injury. 
Martin  du  Magny  (Contribution  a  f£tude  de  V inoculation  tuber- 
culeuse  chez  Vhomme,  These,  Paris,  1886)  has  collected  the  clinical 
material  of  cases  of  inoculation -tuberculosis  and  in  his  comments 
upon  them  asserts  that  the  sputum  of  phthisical  patients  and  animal 
excretions  were  the  usual  carriers  of  contagion,  consequently,  the 
affection  is  most  frequently  met  with  among  physicians,  nurses, 
butchers,  and  teamsters.     The  external  appearances  manifested  at 
the  point  of  inoculation  consist  of  the  formation  of  a  red  nodule 
in  the  skin  which  increases  slowly  in  size  and  forms  a  miliary 
abscess  in  which  papillomatous  proliferation  takes  place,  and  around 
which  a  new  zone  of  infiltration  forms,  which  in  turn  again  sup- 
purates and  becomes  papillomatous.     The  centre  heals  with  the 
formation  of  a  flat  cicatrix,  while  the  destructive  process  progresses 
slowly   in   a   peripheral   direction.     Raymond    (u  Contribution    a 
1'etude  de  la  tuberculose  cutane  par  inoculation  directe,"  France 
Med.,  1886,  p.  99)  reports  two  cases.    In  the  first  case  the  patient, 
suffering  from  advanced  tuberculosis,  inoculated  himself  through 
an  abrasion  of  the  skin  of  the  hand  by  sucking  a  wound  to  arrest 
hemorrhage.    The  little  wound  refused  to  heal,  and  became  covered 
with  a  crust  under  which  suppuration  was  going  on.     Later,  a 
papillomatous  elevation  formed,  which  continued  to  ulcerate  on  the 
surface.     The  margins  of  the  ulcer  were  surrounded  by  an  infil- 
trated zone,  the  skin  covering  it  presenting  a  brownish  color.    The 
second  case,  a  healthy  man,  injured  himself  by  the  prick  of  a  thorn. 


INOCULATION-TUBERCULOSIS.  165 

The  wound  became  infected  with  the  sputum  of  his  phthisical  wife. 
The  puncture  became  the  centre  of  a  papillomatous  swelling  sur- 
rounded by  a  dark  red  zone.  Suppuration  took  place  at  several 
points  at  the  same  time.  The  whole  of  the  diseased  portion  of  the 
skin  was  removed  and  the  sections  taken  from  it,  on  staining, 
showed  the  presence  of  numerous  bacilli.  In  both  cases  the  period 
of  incubation  was  three  weeks. 

Hanot  (Archives  de  Physiologic,  July,  1886)  has  collected  six 
observations  which  would  tend  to  show  that  tubercular  inoculation 
in  man  does  take  place,  one  case  having  fallen  under  his  own 
observation.  In  the  case  observed  by  Hauot,  the  patient  was  in 
the  third  stage  of  phthisis,  and  died  soon  after  with  a  tubercular 
ulcer  on  the  arm  of  at  least  two  years'  standing ;  while  the  history 
of  cough  only  dated  from  the  last  two  months,  which  would  show 
that  the  cutaneous  lesion  preceded  the  pulmonary,  and  was  the 
cause  of  the  phthisis.  In  the  cases  which  he  collected  the  sources 
of  inoculation  were  necropsies  on  tubercular  subjects,  nursing 
phthisical  patients,  handling  old  bones,  pricking  the  hand  with  a 
fragment  of  porcelain  from  the  broken  spittoon  of  a  phthisical 
patient,  and  in  four  of  the  cases  the  tubercular  character  of  the 
cutaneous  lesion  was  verified  by  finding  the  bacilli. 

Axel  Hoist  mentions  the  case  of  an  attendant  on  phthisical 
patients  at  a  hospital,  who  had  suffered  for  a  long  time  from  atonic 
ulceration  of  the  fingers,  which  had  been  treated  unsuccessfully  by 
various  external  applications;  no  tubercle  bacilli  could  be  found 
with  certainty  in  the  sores.  Later,  the  man  was  affected  with 
tuberculous  glandular  swelling  in  the  axilla,  which  contained  a 
considerable  number  of  bacilli,  and  Hoist  considers  that  it  is  highly 
probable  that  the  patient  had  been  infected  through  the  ulcers. 

Merklen  ("  Inoculation  tuberculeuse  localisee  aux  doigts,"  Gazette 
hebd.,  1885,  No.  27)  presented  a  case  of  inoculation  tuberculosis  to 
the  Society  des  hopitaux  in  which  the  infection  of  the  wife  of  a 
phthisical  husband  could  be  clearly  traced,  and  had  occurred 
through  the  fissures  of  the  fingers.  At  the  point  of  inoculation 
hard  nodules  formed  in  which  bacilli  were  found  ;  this  was  followed 
by  tubercular  lymphangitis,  which  finally  led  to  pulmonary  tuber- 
culosis. The  patient  had  previously  been  in  perfect  health  and 
without  any  hereditary  taint. 

Eiselsberg  ("  Beitrage  zur  Impf-tuberculose  beim  Menschen," 
Wiener  med.  Wochenschrift,  1887,  No.  53),  during  the  last  few 
years,  has  observed  four  cases  of  inoculation-tuberculosis.  The  first 
case  was  a  girl  sixteen  years  old,  in  whom  the  disease  developed  in 
the  track  of  a  perforation  of  the  lobe  of  the  ear  made  preparatory 
to  the  wearing  of  an  earring,  and  which  was  kept  from  closing  by 
the  insertion  of  a  thread.  The  tubercular  product  appeared  in  the 


166  TUBEKCULOSIS, 

shape  of  a  hard  swelling  the  size  of  a  hazelnut.  The  second  case 
was  a  young  man  who  injured  himself  with  the  point  of  a  knife 
above  the  external  epicondyle  of  the  humerus.  Eighteen  days  later 
a  swelling  the  size  of  a  pea  appeared  at  the  site  of  injury  with  an 
ulcerated  surface  covered  by  pale  flabby  granulations.  In  the 
axilla  of  the  same  side  one  of  the  lymphatic  glands  was  found 
enlarged  to  the  size  of  a  hazelnut.  The  third  case  concerned  a 
woman  fifty  years  of  age,  who  is  supposed  to  have  infected  herself 
by  washing  the  clothes  of  a  person  the  subject  of  a  tubercular 
abscess  of  the  spine,  and  who  with  her  fingers  scratched  an  acne 
pustule  on  her  face.  At  this  point,  six  to  eight  days  later,  a  pain- 
ful swelling  the  size  of  a  pea  formed  which  subsequently  became  in- 
durated and  opened  spontaneously  in  six  weeks.  At  the  end  of  three 
months  the  place  of  inoculation  presented  an  ulcer  with  indurated 
margins.  In  the  fourth  case  the  inoculation  followed  in  the  track 
made  by  the  needle  of  a  hypodermic  syringe  in  a  girl  twenty  years 
of  age.  The  swelling  opened  after  six  weeks,  and  a  small  quantity 
of  pus  was  discharged.  Four  months,  subsequently,  the  fistulous 
opening  communicated  with  an  abscess  cavity  the  size  of  a  silver 
dollar,  lined  by  a  wall  of  granulation  tissue  In  all  of  these  cases 
no  evidences  of  tuberculosis  could  be  detected  in  any  of  the  inter- 
nal organs,  and  the  local  disease  could  be  traced  in  every  instance 
to  some  antecedent  lesion  through  which  the  infection  had  evidently 
taken  place.  The  diagnosis  in  all  cases  was  based  on  an  examina- 
tion of  the  granulation  tissue  for  the  bacillus  of  tuberculosis,  which 
was  always  found  present. 

Tschering  ("  Inoculations-tuberculose  bei  Menschen,"  Fortschritte 
der  Medicin,  1885,  No.  3)  reports  an  exceedingly  interesting  case 
of  inoculation-tuberculosis  occurring  in  a  person  who  injured  a 
finger  with  a  broken  spittoon  used  by  a  phthisical  patient.  From 
the  little  wound  the  tubercular  infection  extended  to  a  tendon 
sheath  and  later  to  the  axillary  lymphatic  glands. 

Lennander  (Abstract,  Annals  of  Surgery,  June,  1890)  reports  a 
case  of  tuberculosis  of  the  skin  following  vaccination.  The  patient, 
a  student  of  philosophy,  thirty-five  years  old,  presented  tubercu- 
losis of  the  skin  of  the  right  upper  arm.  The  lesion  had  developed 
after  the  first  vaccination,  and  later  extended  over  a  larger  part  of 
the  upper  arm.  After  repeated  curetting  and  cauterizing  the  place 
healed  over  finally  after  grafting  by  Thiersch's  method. 

I  have  seen  a  number  of  cases  of  well-marked  tuberculosis  of 
the  skin  in  which  the  diagnosis  was  verified  by  inoculation  experi- 
ments and  microscopical  examination  in  every  instance.  I  had 
every  reason  to  suspect  that  the  lesions  were  the  result  of  cutaneous 
inoculation.  I  also  had  under  treatment  a  well-marked  case  of 
extensive  subcutaneous  tuberculosis  of  the  hand  in  the  person  of 


INOCULATION— TUBEECULOSIS.  167 

the  mother  of  several  children,  who  had  died  of  pulmonary  tuber- 
culosis. The  disease  originated  near  the  tip  of  the  index  finger  at 
the  site  of  a  former  abrasion  in  which  a  papillomatous  swelling 
formed.  This  ulcerated  and  partly  healed,  when  the  disease  com- 
menced to  spread  along  the  subcutaneous  connective-tissue,  and  had 
extended  almost  over  the  entire  dorsum  of  the  hand  at  the  time 
she  came  under  my  care.  A  number  of  fistulous  openings  existed 
which  discharged  only  a  few  drops  of  thin,  serous  pus  daily.  The 
subcutaneous  tissue  was  transformed  into  a  mass  of  granulation 
tissue  which  was  removed  after  free  incision  with  a  Volkmanu's 
spoon,  and  the  wound  surfaces  were  freely  iodoformized.  The 
process  of  repair  was  slow  but  satisfactory. 

TUBERCULAR  INFECTION  OF  WOUNDS. — Eiselsberg's  case  has 
already  been  described  in  which  tubercular  infection  took  place 
through  a  small  punctured  wound  of  the  arm. 

Middeldorpff  ("Ein  Fall  von  Infection  einer  penetrireuden 
Kniegelenks-Wunde  durch  tuberculoses  Virus,"  Fortscliritte  der 
Medicin,  1886)  reports  the  case  of  a  healthy  carpenter  who  opened 
his  knee-joint  by  the  cut  of  an  axe,  and  dressed  the  wound  with  a 
soiled  handkerchief.  The  wound  healed  kindly,  but  later  the  joint 
became  swollen,  tender,  and  painful.  Resection  was  performed, 
and  on  examining  the  capsule  it  was  found  very  much  thickened. 
In  the  granulation  tissue  bacilli  were  found. 

Czerny  (Centralblatt  f.  Chirurgie,  1886)  reports  two  cases  in 
which  tuberculosis  followed  in  wounds  treated  by  Reverdin's  trans- 
plantation of  skin.  In  both  instances  the  patients  were  healthy, 
and  the  skin  transplantation  was  made  during  the  treatment  of 
extensive  burns.  The  skin  was  taken  from  limbs  amputated  for 
tubercular  affections.  In  both  cases  tuberculosis  of  the  adjacent 
joint  occurred  and  in  one  of  them  tuberculosis  of  the  granulating 
surface. 

A  case  of  tubercular  infection  through  earrings  is  related  (  Wiener 
med.  Presse,  1889)  in  a  girl,  fourteen  years  of  age,t)f  a  perfectly 
healthy  family,  who  wore  earrings  left  to  her  by  a  friend  who  had 
died  of  pulmonary  tuberculosis.  Soon  ulcers  appeared  on  the  lobes 
of  both  ears,  the  cervical  glands  became  swollen,  and  percussion  and 
auscultation  revealed  infiltration  of  the  apex  of  the  left  lung.  Tuber- 
cle bacilli  were  found  in  the  ulcers  and  sputa.  This  case  is  only 
another  instance  of  inoculation-tuberculosis  where  from  the  point 
of  injection  the  disease  extended  along  the  lymphatic  system  and 
finally  systemic  infection  occurred  from  the  entrance  of  the  bacilli 
into  the  general  circulation. 

Wahl  ("  Mittheilungen  eines  Falles  von  Inoculations  Tuberculose 
nach  Amputation  des  Unterarms,"  Verh.  der  Deutsehen  Gesellschaft 
/.  Chirurgie,  XV.  Congress)  amputated  the  arm  of  a  boy  suffering 


168  TUBEKCULOSIS. 

from  gangrene,  the  result  of  an  injury,  and  discharged  the  patient 
with  the  wound  completely  healed,  except  a  small  granulation  sur- 
face from  which  the  drainage-tube  had  been  removed.  At  home 
the  wound  was  dressed  by  a  girl  suffering  from  tuberculosis.  The 
wound  showed  soon  all  the  characteristic  appearances  of  fungous 
disease,  and  the  lymphatic  glands  became  infected  from  this  source. 

Konig  (Die  Chirurgische  Klinik  in  Gottingen,  Leipzig,  1882)  has 
observed  sixteen  cases  of  inoculation-tuberculosis  following  opera- 
tions for  tuberculous  disease  of  bones,  and  two  such  cases  have  been 
described  by  Kraske  ("  Ueber  tuberculose  Erkrankuug  der  "Wun- 
den,"  Centralblattf.  Chirurgie,  1885,  p.  565). 

INOCULATION  FOLLOWING  CIRCUMCISION. — A  number  of  cases 
of  inoculation-tuberculosis  following  circumcision  are  on  record  in 
which  the  infection  often  occurred  in  the  practice  of  orthodox  Jews, 
who  performed  the  operation  in  accordance  with  the  directions  laid 
down  in  the  Mosaic  laws.  The  loose  connective-tissue  of  the  pre- 
puce, richly  supplied  with  lymphatics,  is  an  admirable  surface  for 
absorption,  and  when  brought  in  contact  with  infectious  material 
would  furnish  the  most  favorable  conditions  for  the  production  of 
local  lesions  and  the  transportation  of  microbes  along  the  lymphatic 
channels  to  more  distant  parts. 

Lehmann  ("  Ueber  einen  Modus  der  Impftuberculose  beim  Men- 
chen,"  Deutsche  med.  Wochensehrift,  1886)  has  observed  ten  cases 
of  inoculation-tuberculosis  in  Jewish  boys  caused  by  sucking  the 
wound  after  ritual  circumcision  by  a  phthisical  person.  Ten  days 
after  circumcision  the  wound  became  the  seat  of  ulceration,  and  the 
inguinal  glands  began  to  enlarge.  Four  of  the  children  died  of 
tubercular  meningitis,  and  three  died  after  a  prolonged  illness 
caused  by  multiple  tubercular  abscesses. 

Hofmokl  has  reported  a  similar  case,  and  Weichselbaum  detected 
the  bacillus  of  tuberculosis  in  the  circumcision  wound. 

Elsenberg  (Centralblatt  f.  Bacteriologie  u.  Parasitenkunde,  B.  ii. 
S.  577)  has  'described  three  new  cases  of  inoculation-tuberculosis 
after  circumcision.  All  the  cases  were  infants,  and  the  disease 
appeared  primarily  in  the  wound,  or  cicatrix,  and  later,  in  the 
inguinal  glands.  Local  treatment  by  evidemeut  proved  successful. 
The  diagnosis  was  corroborated  by  microscopical  examination  of  the 
granulation  tissue. 

Meyer  ("  Em  Fall  von  Impftuberculose  in  Folge  ritueller  Cir- 
cumcision," New  Yorker  Med.  Presse,  June,  1887)  reports  a  case 
in  which  circumcision  was  performed  according  to  the  rites  of  the 
church  eight  days  after  birth  by  an  old  man,  and  in  which  four 
weeks  after  the  operation  an  induration  appeared  at  the  frenulum 
and  the  inguinal  glands  about  the  same  time  began  to  enlarge. 
Syphilis  was  suspected,  and  the  patient  was  put  on  a  specific  course 


INOCULATION-TUBERCULOSIS.  169 

of  treatment.  The  inguinal  glands  suppurated  and  another  small 
abscess  formed  in  the  right  gluteal  region.  The  diseased  tissue 
about  the  glans  penis  was  excised.  Microscopical  examination  of 
the  granulations  revealed  the  presence  of  miliary  tubercles  and 
bacilli  in  great  abundance.  The  above  cases  furnish  abundant 
proof  of  the  possibility  of  the  transmission  of  tuberculosis  by  cutane- 
ous inoculation  through  abraded  surfaces,  small  wounds,  and  granu- 
lating surfaces,  and  deserve  the  most  careful  attention  of  surgeons 
in  the  matter  of  prophylaxis,  diagnosis  and  treatment. 


CHAPTEE    XVII. 

CLINICAL  FORMS  OF  SURGICAL  TUBERCULOSIS. 

IT  is  but  a  few  years  ago  since  the  forms  of  tuberculosis  to  which 
allusion  will  be  made  here  were  not  correctly  understood,  and  con- 
sequently a  rational  surgical  treatment  was  out  of  the  question. 
Most  all  of  the  localized  tubercular  processes  were  included  under 
the  general  term  scrofula,  and  were  looked  upon  as  local  manifesta- 
tions of  a  general  dyscrasia,  and  treated  in  accordance  with  this 
view  of  their  pathology.  The  discovery  of  the  bacillus  of  tuber- 
culosis has  rendered  the  word  scrofula  obsolete,  and  has  assigned  to 
the  tubercular  processes  in  the  various  organs  and  tissues  of  the 
body  their  correct  etiological  and  pathological  significance  and 
paved  the  way  for  their  successful  surgical  treatment. 

1.  Skin. 

a.  Tuberculosis  verrucosa  cutis.     Riehl  u.  Paltauf  ("Tubercu- 
losis verrucosa  cutis/7  Vierteljahrsschrift  f.  Dermatologie  u  Syphilis, 
B.  xiii.  S.  14)  have  described  an  affection  of  the  skin,  under  the 
name  of  tuberculosis  verrucosa   cutis,   in   which   the   bacillus  of 
tuberculosis  was  constantly  found,   and  which  they  attributed  to 
local  infection,  because  all  of  the  patients  they  examined  were 
persons  handling  animal  products.     Riehl  ("  Tuberkel  Bacillen  in 
einem   sogenannten    Leicheu-tuberkel,"    Centralblatt  f.    Chirurgie, 
1885,  No.  32)  has  shown,  by  finding  the  tubercle  bacillus  in  the 
warty  affections  of  pathological  anatomists,  the  probable  tuberculous 
nature  of  this  condition  of  the  skin,  although  the  infection  may  be 
a  mixed  one. 

b.  Lupus.     The  long  debate  which  has  been  carried  on  for  years 
as  to  the  identity  or  non-identity  of  lupus  and  tuberculosis  has  ter- 
minated in  favor  of  those  who  argued  that  lupus  is  a  tuberculosis 
of  the  skin,  hence  the  term  lupus  should  be  omitted  from  nomen- 
clature, and  the  term  tuberculosis,  as  applied  to  the  skin  and  mucous 
surfaces,  should  be  qualified  by  the  anatomical  name  of  the  surface 
affected. 

Finger  ("  Lupus  und  Tuberculose,"  Centralblatt  f.  Bacteriologie 
u.  Parasitenkundej  B.  xi.  S.  348),  in  a  lengthy  and  able  article, 
makes  a  careful  inquiry  into  the  identity  of  lupus  and  tuberculosis, 
and  after  a  careful  review  of  all  that  pertains  to  this  subject  decides 


TUBERCULOSIS    OF    THE    SKIN.  171 

in  favor  of  its  tubercular  origin  and  character.  He  alludes  to  the 
views  of  Hebra,  Virchow,  Klebs,  Hueter,  and  others.  From  a 
clinical  standpoint  Hebra  brought  the  different  varieties  of  lupus 
under  one  common  head.  He  separated  it  entirely  from  syphilis, 
but  otherwise  did  little  to  fix  its  pathological  significance.  He 
adopted  the  classification  of  Fuchs,  and  the  older  French  and 
English  authors,  who  taught  that  it  was  one  of  the  manifestations 
of  scrofula,  and  that  anatomically  it  was  composed  of  granulation 
tissue.  Yirchow  classified  it  with  the  granulomata,  but  denied  its 
identity  with  scrofula.  Rindfleisch  described  it  as  a  proliferation 
of  epithelial  cells,  as  a  sort  of  phthisis  cutauea.  Eppinger  referred 
to  it  as  a  product  of  connective-tissue  growth  and  proposed  its 
classification  with  carcinoma.  Klebs  looked  upon  it  as  a  specific 
affection,  and  histologically  included  it  among  the  small-celled  leu- 
cocytoses.  Hueter,  who  in  his  pathological  views  was  generally  far 
in  advance  of  his  time,  affirmed  that  it  was  a  form  of  fungous 
inflammation,  the  specific  cause  of  which,  when  introduced  into  the 
organism,  produced  a  miliary  tuberculosis.  Volkmaun  included  it 
among  the  affections  composed  of  granulation  tissue.  Friedlander 
("  Ueber  locale  Tuberculose,"  Volkmann's  Klinische  Vortrdge, 
1881,  No.  31)  was  the  first  to  take  a  positive  stand  in  asserting  that 
lupus  is  a  tubercular  affection  of  the  skin,  and  showed  its  histologi- 
cal  identity  with  other  recognized  forms  of  local  tuberculosis.  He 
demonstrated  the  presence  of  miliary  tubercles  in  it,  and  that  these 
nodules  were  composed  of  giant  and  epithelial  cells,  the  same  as  in 
tubercles  of  the  lungs.  The  views  entertained  by  Baumgarten  as 
to  the  histological  structure  of  lupus  are  different  from  those  just 
described.  He  believed  that  in  the  miliary  tubercle  the  abundance 
of  epithelioid  cells  predisposed  to  caseation  and  suppuration,  while 
he  recognized  in  lupus,  as  the  most  characteristic  distinguishing 
features,  absence  of  caseation  and  suppuration  and  the  presence  of 
cicatricial  tissue.  He  admits,  at  the  same  time,  that  lupus  may  be 
closely  allied  to  tuberculosis. 

Schiiller  ("  Ueber  die  Stellung  des  Lupus  zur  Tuberculose," 
Centralblatt  f.  Chirurgie,  1881)  opposed  Baumgarteu  and  empha- 
sized the  fact  that  caseation,  characteristic  as  it  might  be  for  all 
tuberculous  affections,  always  constitutes  only  a  secondary  condition 
and  depends  upon  the  soil  present  in  and  around  the  nodule.  The 
absence  of  caseation  in  lupus,  which  in  rare  cases,  however,  has 
been  shown  to  be  present  by  Cohuheim  and  Thoma,  could  not  be 
urged  as  a  positive  and  infallible  diagnostic  criterion  of  the  non- 
tubercular  nature  of  lupus. 

Neisser  (Die  chronische  Infections- Krankheiten  der  Haut,  Ziems- 
sen,  B.  xiv.,  1882)  accepts  fully  and  pleads  strongly  in  favor  of 
the  tubercular  nature  of  lupus.  In  the  meantime  Pantlen,  Bizzo- 


172      CLINICAL    FOKMS    OF    SURGICAL    TUBERCULOSIS. 

zero,  Baumgarten,  Chiari,  Hall,  Janisch,  Riehl,  Vidal,  and  Finger 
described  a  new  affection,  a  diffuse  tuberculosis  of  the  skin  and 
mucous  membranes,  occurring  as  a  sort  of  secondary  localization  in 
patients  suffering  from  advanced  tuberculosis.  To  prove  that 
lupus  and  tuberculosis  are  identical  it  became  necessary  to  furnish 
the  necessary  experimental  proof,  and  to  show  the  uniform  pres- 
ence of  the  bacillus  of  tuberculosis  in  the  lupus  tissue.  The  inocu- 
lation experiments  with  lupus  tissue  have  already  been  mentioned, 
and  from  them  it  can  be  learned  that  with  few  exceptions  they 
were  followed  by  positive  results  ;  that  is  to  say,  implantation  of 
lupus  tissue  into  the  subcutaneous  tissue  or  peritoneal  cavities  of 
animals  susceptible  to  tuberculosis  gave  rise  to  local  tuberculosis  at 
the  point  of  implantation,  and  to  dissemination  of  the  process  in  a 
manner  characteristic  of  tuberculosis  in  man. 

Demme  ("  Lupus  uud  Tuberculose,"  Wurzburger  med.  Blcitt., 
1887)  reports  two  cases  of  cutaneous  inoculation-tuberculosis  in 
man.  The  first  case,  a  nurse  girl,  contracted  an  ulcerating  lupus 
from  a  child  three  years  of  age  which  died  of  tubercular  ulceration 
of  the  tonsils,  and  tuberculosis  of  other  organs.  The  second  case 
was  a  child  with  eczema  which  slept  in  the  same  bed  with  its 
phthisical  mother.  Sections  of  the  eczematous  skin,  stained  and 
examined  under  the  microscope,  showed  numerous  bacilli.  The 
child  died  later  of  hemorrhage  of  the  stomach,  the  cause  of  which 
at  the  necropsy  was  shown  to  be  a  tuberculous  ulcer  of  the  stomach. 

Demme  enumerates  the  following  reasons  as  showing  the  identity 
of  lupus  and  tuberculosis  : 

1.  Similarity  of  histological  structure. 

2.  Presence  of  the  bacillus  of  tuberculosis  in  the  granulation 
tissue  of  lupus. 

3.  The  production  of  typical  tuberculosis  in  animals  not  immune 
to  this  disease  by  implantation  of  lupus  tissue,  or  injection  of  a 
pure  culture  of  the  bacillus  of  tuberculosis  obtained  from  lupus 
tissue. 

4.  The  fact  that   patients  suffering  from    lupus  are  frequently 
attacked  by  and  die  of  tuberculosis  of  other  organs. 

5.  The  prevalence  of  tubercular  affections  among  relatives  suf- 
fering from  lupus  (hereditary  predisposition). 

Boeck  has  made  the  statement  that,  of  sixteen  cases  of  lupus, 
three  die  subsequently  of  pulmonary  and  general  miliary  tubercu- 
losis. Heiberg  reports  death  from  tubercular  meningitis  in  a 
lupus  patient. 

Rassdnitz  ("  Zur  Aetiologie  des  Lupus  vulgaris,"  Vierteljahrs- 
schriftf.  Dermat.  und  Syphilis,  1882)  collected  209  cases  of  lupus 
and  found  that  in  thirty  per  cent,  of  all  the  cases  it  was  associated 
with  other  evidences  of  tuberculosis.  He  placed,  also,  great 


TUBERCULOSIS    OF    THE    SKIN.  173 

importance  on  the  observations  that  lupus  is  prone  to  develop  in 
the  scar  left  after  the  healing  of  a  localized  tuberculosis  in  lym- 
phatic glands,  and  that  lupus  is  often  observed  upon  the  nose  or 
eyelids  in  cases  of  chronic  nasal  or  conjunctival  catarrh.  In  ten  to 
fifteen  per  cent,  of  his  cases  lupus  could  be  traced  to  a  hereditary 
predisposition.  Demme  observed  miliary  tuberculosis  in  two  of 
his  cases  after  scraping  lupus.  Pontoppindau  asserted  that,  in  his 
experience,  in  fifty  to  seventy-five  per  cent,  the  patients  manifested 
additional  evidences  of  tuberculosis. 

Quinquaud  (De  le  Scrofule,  These,  Paris,  1880)  saw  in  three 
cases  of  lupus  pulmonary  tuberculosis  appear  as  the  final  cause  of 
death. 

Of  thirty-eight  cases  that  came  to  the  personal  knowledge  of 
Bessnier  (Le  Lupus  et  son  Traitement.  Ann.  de  Dermat.,  1883), 
eight  of  them  suffered  from  pulmonary  phthisis.  Of  two  patients 
treated  by  Aubert,  one  died  of  acute  pulmonary  tuberculosis,  and 
the  other  of  tubercular  pleuritis  after  scarification,  Renouard  was 
able  to  ascertain  the  existence  of  pulmonary  phthisis  in  fifty  per 
cent,  of  his  cases  of  lupus. 

Block  ("  Klinische  Beitrage  zur  Aetiologie  u.  Pathogenese  des 
Lupus,"  Vierteljahrsschrift  f.  Dermat.  u.  Syphilis,  1886)  met  with 
tuberculosis  in  other  organs  before  or  after  the  development  of 
lupus,  in  114  out  of  144  cases.  Bender  (u  Ueber  die  Beziehungen 
des  Lupus  vulgaris  zur  Tuberculose,"  Eerl.  klin.  Wochenschrift, 
1886)  examined  374  cases  of  lupus.  In  159  of  these  cases  an 
accurate  account  could  be  obtained.  In  99  of  the  latter  number 
symptoms  of  other  antecedent  or  coexisting  tuberculous  lesions 
existed.  In  77  of  the  cases  tuberculosis  in  an  etiological  or  clinical 
aspect  was  present. 

Leloir  ("Recherches  nouvelles  sur  les  relations  qui  existent 
entre  le  lupus  vulgaris  et  la  tuberculose,  "  Annal.  de  Dermat.  et 
Syphilis,  I.,  viii.)  observed  several  cases  in  which  after  years  a 
lupus  of  the  face  gave  rise  to  a  pseudo-erysipelatous  swelling  of  the 
face  which  disappeared  after  a  time,  to  be  followed  by  swelling  of 
the  submaxillary  lymphatic  glands,  which  remained  stationary. 
Soon  after  the  affection  of  the  lymphatic  glands  had  appeared, 
febrile  disturbances,  gastric  symptoms,  and  evidences  of  pulmonary 
infiltration  followed.  In  all  of  these  cases,  Leloir  believes  that 
the  virus  of  tuberculosis  had  left  the  primary  location  and  had 
migrated  through  the  lymphatic  vessels  and  glands  into  the  lungs. 
In  ten  out  of  his  seventeen  cases,  the  tubercular  nature  of  lupus 
was  clinically  manifest. 

Sachs  (Beitrage  zur  Statistic  des  Lupus,"  Centralblatt  f.  Chi- 
rurgie,  1887,  No.  2,  p.  19)  ascertained  that  of  105  cases  of  lupus 
which  he  had  collected,  in  eighty-six  per  cent,  the  patients  had 


174      CLINICAL    FOKMS    OF    SUKGICAL    TUBERCULOSIS. 

coexisting  tuberculosis  in  other  parts  of  the  body,  or  a  hereditary 
predisposition  to  tuberculosis  could  be  shown  to  exist. 

The  above  literature  furnishes  strong  clinical  evidence  of  the 
identity  of  lupus  with  tuberculosis,  but  the  following  bacteriologi- 
cal researches  furnish  the  final  and  conclusive  proof.  Koch  in  his 
paper  on  the  etiology  of  tuberculosis  (previously  quoted)  states  that 
he  produced  a  pure  culture  of  the  bacillus  of  tuberculosis  from  a 
case  of  lupus  which  resembled  in  every  respect  the  culture  obtained 
from  recognized  tubercular  lesions,  and  with  the  fifteenth  genera- 
tion from  this  source,  one  year  after  the  first  cultivation,  he  inocu- 
lated five  guinea-pigs  by  subcutaneous  injection,  and  produced 
typical  tuberculosis  in  all  of  them. 

Doutrelepont  ("  Tuberkel-bacillen  im  Lupus,"  Monatschrift  /. 
prald.  Dermatologie,  1883),  in  seven  cases  of  lupus,  found  the  bacillus 
of  tuberculosis  invariably  present  in  greater  or  less  number,  either 
within  the  cells,  or  dispersed  in  small  groups  between  them.  He 
never  found  them  in  giant  cells,  but  in  their  immediate  vicinity. 
In  a  second  paper  the  same  author  (u  Zur  Therapie  des  Lupus/' 
Monatschrift  f.  prakt.  Dermatologie,  1884)  reports  eighteen  addi- 
tional cases  of  lupus,  in  each  of  which  the  presence  of  the  bacillus 
could  be  demonstrated. 

Demme  ("  Zur  diagnostischeu  Bedeutung  der  Tuberkel-bacillen 
fur  das  Kindesalter,"  Berl.  Idin.  Wochenschrift,  1883)  in  six  cases 
of  lupus  detected  the  bacillus  of  tuberculosis.  Pfeiifer  ("  Tuberkel- 
bacillen  in  der  lupos  erkrankten  Conjunctiva/7  Berl.  klin.  Wochen- 
schrift^ 1883)  demonstrated  the  presence  of  the  specific  microbic 
cause  of  tuberculosis  in  a  case  of  lupus  of  the  conjunctiva. 

Schuchardt  and  Krause  ("  Ueber  das  Vorkommen  der  Tuberkel- 
bacillen  bei  fungosen  und  scrofulosen  Entziindungen,"  Fortschritte 
der  Meditin,  1883)  found  the  bacillus  of  tuberculosis  in  three  cases 
of  lupus  affecting  the  face,  ears,  and  legs.  In  examinations  made 
of  eleven  cases  of  lupus  by  Cornil  and  Leloir,  and  four  by  Koch 
for  the  especial  purpose  of  showing  the  identity  of  lupus  and  tuber- 
culosis, the  bacillus  was  found  in  every  instance.  In  the  artificial 
tuberculosis  of  animals  produced  by  implantation  of  lupus  tissue, 
the  bacillus  of  tuberculosis  was  shown  to  exist  by  Pagenstecher, 
Pfeiffer,  Koch,  and  Doutrelepont. 

2.  Primary  Tuberculosis  of  Iris. 

Griffith  (British  Medical  Journal,  Dec.  21,  1889)  has  related  a 
case  of  primary  tuberculosis  of  the  iris  which  occurred  in  a  seven 
months'  old  female  child.  The  eye  had  been  affected  for  one  month ; 
there  was  an  enlarged  gland  in  the  neck  on  the  same  side,  but  there 
were  no  other  physical  signs  of  tubercle.  No  history  of  heredity. 


TUBERCULOSIS    OF    THE    LYMPHATIC    GLANDS.          175 

A  yellowish  nodule  grew  from  the  periphery  of  the  iris  of  the 
right  eye.  and  numerous  millet-seed  bodies  from  its  surface ;  the 
pupil  was  closed,  but  there  was  no  acute  inflammation.  The  local 
disease  increased  rapidly  in  extent.  The  eye  was  enucleated  after 
three  weeks'  treatment.  The  disease  was  found  to  be  confined  to 
the  iris  and  ciliary  body.  Under  the  microscope  the  new-growth 
showed  the  characteristic  structure  of  tubercle.  In  32  recorded 
cases  in  which  microscopic  and  bacteriological  tests  left  no  doubt 
as  to  the  tubercular  nature  of  the  disease,  one  eye  only  was  affected 
in  29 ;  the  average  age  of  the  patients  was  twelve,  youngest  four 
months,  oldest  fifty-one  years.  In  10  cases  bacilli  were  searched 
for,  but  only  found  in  4  ;  in  one  of  the  remaining  6  cases,  however, 
the  inoculation  test  was  successful.  A  number  of  patients  recovered 
completely  and  permanently  after  enucleatiou. 

3.   Tuberculosis  of  the  Internal  Ear. 

That  an  ordinary  otitis  media  with  perforation  of  the  tympanum 
may  occasionally  be  transformed  into  a  tubercular  lesion  by  the 
entrance  from  without  of  bacilli  of  tuberculosis  there  can  be  no 
doubt.  Habermanu  (Prager  med.  Wochenschrift,  March  7,  1888) 
has  recently  investigated  this  subject  by  examining,  post-mortem, 
18  tuberculous  subjects  in  whom  either  otorrhoea  or  deafness  without 
active  discharge  had  been  observed  during  life,  and  in  nine  of  these 
he  could  demonstrate  the  presence  of  tubercular  lesions  in  the 
auditory  canal.  In  one  case  he  found  in  the  left  auditory  appara- 
tus tuberculosis  of  the  entire  middle  ear,  where  the  tympanum  was 
intact.  In  another  tubercular  subject,  a  man,  thirty-eight  years  of 
age,  in  whom  tuberculosis  of  the  ear  was  observed  a  year  and  a 
half  before  death,  the  post-mortem  revealed  extensive  tuberculosis 
of  the  cochlea,  in  the  internal  auditory  canal,  and  in  the  superior 
semicircular  canal,  while  the  other  semicircular  canals  and  the 
vestibule  were  destroyed  by  caries. 

4.  Lymphatic  Glands. 

That  most  cases  of  chronic  inflammation  of  the  lymphatic  glands 
are  in  their  origin,  course,  and  final  termination,  cases  of  local 
tuberculosis  has  been  satisfactorily  shown  by  clinical  experience, 
inoculations,  and  cultivation  experiments.  The  tubercular  virus 
enters  the  lymphatic  circulation  undoubtedly  most  frequently 
through  some  superficial  abrasion,  ulceration,  eczema,  or  some 
other  affection  of  the  skin,  as  any  loss  of  continuity  of  surface 
may  furnish  the  necessary  portio  invasionis  for  the  entrance  of 
bacilli  from  without.  Yolkmann  found  tubercle  bacilli  in  the 
skin  of  an  eczematous  forearm.  In  perhaps  95  out  of  100  cases 


176      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

of  tuberculosis  of  the  lymphatic  glands  the  disease  attacks  the 
glands  of  the  neck,  as  the  scalp,  face,  and  mouth  are  parts  of 
the  body  frequently  the  seat  of  slight  injuries  and  superficial 
lesions,  and  consequently  often  exposed  to  tubercular  infection. 
The  lymphatic  glands  are  filters  for  the  microbes  which  enter  the 
body  through  the  lymphatic  vessels  The  pathological  conditions 
which  are  produced  in  the  interior  of  a  lymphatic  gland  by  the 
presence  of  pathogenic  microorganisms  are  well  calculated,  for  the 
time  being,  at  least,  to  limit  the  affection.  The  lymphadenitis 
which  is  produced  blocks  the  lymph  spaces  with  the  products  of  a 
specific  inflammation  which  temporarily  at  least  mechanically  fixes 
the  microbes  in  their  location.  Primary  infection  of  a  lymphatic 
gland  by  the  bacillus  of  tuberculosis  in  many  instances  attacks  dif- 
ferent portions  of  the  gland  from  the  very  beginning,  as  a  number 
of  independent  centres  of  tissue-proliferation  are  established  around 
each  microbe  which  has  become  arrested  on  its  way  through  the 
gland.  These  separate  nodules  soon  become  confluent  and  form  a 
mass  of  considerable  size,  which  soon  implicates  the  entire  paren- 
chyma of  the  gland.  Local  diffusion  of  the  bacillus  of  tubercu- 
losis in  the  interior  of  the  gland  is  accomplished  by  the  assistance 
of  the  lymph  stream  as  long  as  the  bacillus  remains  free,  and 
through  the  medium  of  cells  as  soon  as  it  has  become  mtra-cellular. 
Local  infection  is  not  limited  to  the  lymphatic  glands  on  the  proxi- 
mal side  of  the  primary  focus,  as  during  the  course  of  the  disease 
we  often  observe  that  lymph  glands  become  involved  which  are 
not  in  the  direct  course  of  the  lymphatic  circulation.  As  the 
bacillus  of  tuberculosis  is  non-motile,  we  can  only  explain  its  trans- 
portation in  a  direction  opposite  the  lymph  current  by  its  convey- 
ance in  such  a  direction  by  migrating  cells.  The  usual  course  of 
infection  along  the  lymphatic  channels  is,  however,  in  the  direction 
of  the  lymph  current.  The  course  of  the  disease  is  almost  charac- 
teristic. A  lymphatic  gland  in  the  submaxillary  or  parotid  region 
becomes  enlarged,  and  from  this  centre  the  infection  invades  suc- 
cessively gland  after  gland,  until  the  whole  chain  of  lymphatics 
from  the  lower  jaw  to  the  clavicle  has  become  involved.  Another 
interesting  feature  is  observed  in  reference  to  the  regional  diffusion 
of  the  tuberculous  process,  as  the  course  of  infection  usually  corre- 
sponds to  the  location  of  the  gland  first  affected.  If  the  infection 
has  involved  primarily  one  of  the  deep  glands  of  the  neck,  the 
glands  subsequently  invaded  belong  to  the  deep  lymphatics  which 
follow  the  large  vessels  of  the  neck.  If,  on  the  other  hand,  the 
primary  infection  is  located  in  one  of  the  superficial  glands  which 
are  being  irrigated  by  the  lymph  which  flows  through  and  from 
this  gland  become  the  seat  of  successive  infection,  showing  again 
that  regional  infection  usually  takes  place  in  the  direction  of  the 


TUBERCULOSIS    OF    THE    LYMPHATIC    GLANDS.       177 

lymph  current.  As  long  as  the  infection  has  not  extended  along 
the  entire  length  of  the  chain  of  lymphatic  glands  the  patient  is 
protected  against  miliary  tuberculosis,  but  as  soon  as  the  virus  has 
passed  all  the  lymphatic  filters,  and  has  direct  access  into  the  tho- 
racic duct,  miliary  tuberculosis  follows  as  an  inevitable  result  by  the 
entrance  of  the  bacilli  into  the  general  circulation. 

Weigert  ("  Die  Verbreitungswege  des  Tuberkelgifts  nach  dessen 
Eintritt  in  den  Organismus,"  Jahrb.  f.  Kinderheilkunde,  B.  xxi.  S. 
146),  in  his  description  of  the  process  of  dissemination  in  cases  of 
acute  miliary  tuberculosis,  has  pointed  out  that  in  some  cases  the 
bacilli  are  conveyed  through  the  lymphatic  system  successively 
until  they  reach  the  general  circulation,  while  in  others,  and  by  far 
the  greater  number,  generalization  of  the  tuberculous  process  takes 
place  more  directly  by  the  entrance  of  tubercular  products  through 
a  vein,  an  occurrence  which  is  followed  at  once  by  rapid  and  exten- 
sive diffusion  by  embolism.  When  the  bacilli  of  tuberculosis  have 
reached  the  systemic  circulation,  the  intensity  of  symptoms  and  the 
subsequent  course  of  the  disease  depend  on  the  number  of  bacilli 
which  the  blood  contains. 

Weichselbaum  ("  Ueber  Tuberkel-bacillen  im  Blute  bei  allge- 
meiner  acuter  Miliartuberculose,"  Anz.  d.  ges.  Wimerarzte,  1384, 
No.  1 9),  starting  with  the  idea  advanced  by  Weigert  that  every 
acute  miliary  tuberculosis  is  caused  by  the  direct  entrance  of  the 
tuberculous  virus  into  a  vein  or  indirect  entrance  along  the  lym- 
phatic channels  and  through  the  thoracic  duct  into  a  vein,  examined 
the  blood  of  three  such,  and  found  that  it  contained  numerous  bacilli. 
In  the  lymphatic  glands  the  tubercular  process  pursues  a  typical 
pathological  course.  According  to  the  rapidity  of  tissue-prolifera- 
tion, or  in  proportion  to  the  number  of  bacilli  present,  the  granu- 
lation tissue  which  is  always  the  first  and  constant  product  of 
tubercular  inflammation  undergoes  caseation,  and  at  an  early  stage 
often  numerous  centres  can  be  seen  from  where  the  retrograde 
degenerative  changes  take  their  starting-point.  By  confluence  of 
such  caseous  foci  the  entire  gland  is  formed  into  a  cheesy  mass. 
Liquefaction  of  such  caseous  material  results  in  the  formation 
of  a  fluid  which  macroscopically  resembles  pus,  but  under  the 
microscope  it  presents  only  the  product  of  retrograde  tissue-trans- 
formation, and  no  well-defined  pus  corpuscles,  and  none  of  the 
microorganisms  which  are  known  to  produce  suppuration  can  be 
obtained  by  cultivation  experiments,  showing  conclusively  that  the 
fluid  possesses  no  pyogeuic  properties.  The  bacillus  of  tuberculosis 
finds  in  the  granulation  tissue  a  soil  well  adapted  to  its  growth  and 
development,  but,  as  soon  as  caseation  takes  place,  its  culture  soil 
in  that  portion  of  the  gland  has  been  destroyed,  and  its  field  of 
growth  is  limited  to  the  surrounding  zone  of  granulation  tissue,  in 

12 


178      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

which  it  can  be  constantly  found,  while  it  is  absent  in  the  central 
mass,  or,  at  least,  only  an  isolated  rod  can  be  found  here  and  there 
on  patient,  careful  search.  In  all  probability  the  death  of  the 
granulation  tissue  which  precedes  caseation  is  caused  by  the  action 
of  the  ptomaines  of  the  bacilli  of  tuberculosis,  which  by  their  toxic 
properties  destroy  the  protoplasm  and  arrest  further  cell-growth  in 
that  portion  of  the  gland  as  well  as  reproduction  of  the  micro- 
organisms. When  a  true  suppuration  takes  place  in  a  tubercular 
lymphatic  gland,  it  does  so  in  consequence  of  a  secondary  infection 
with  pyogenic  microorganisms.  A  spontaneous  and  permanent  cure 
is  not  infrequently  effected  by  the  substitution  of  an  acute  suppura- 
tive  process  in  place  of  the  primary  specific  chronic  inflammation, 
which  destroys  the  entire  soil  of  the  bacillus  of  tuberculosis,  and, 
at  the  same  time,  effects  complete  elimination  of  the  pus-microbes 
and  the  bacilli  through  the  discharges  of  the  abscess.  The  capsule 
of  the  gland  furnishes  an  efficient  protection  wall  to  the  para- 
glandular  tissues  against  tubercular  infection  often  for  months  and 
years,  but  when  perforation  has  once  taken  place  the  disease  attacks 
the  surrounding  tissues  irrespective  of  their  anatomical  structure. 
When  a  tubercular  gland  becomes  the  seat  of  an  acute  suppuration, 
the  suppurative  inflammation  appears  in  the  form  of  a  para-adenitis 
with  suppuration  between  the  gland  and  the  surrounding  tissues, 
which  often  terminates  in  extensive  separation  of  the  gland  from 
the  adjacent  tissues.  While  tuberculosis  of  the  lymphatic  glands 
often  stands  in  a  direct  causative  relationship  to,  and  precedes  gen- 
eral, diffuse,  and  pulmonary  tuberculosis,  it  is  seldom  observed  as 
a  secondary  affection  in  the  course  of  tuberculous  affections  of  other 
organs.  Tuberculosis  of  the  lymphatic  glands  is  an  affection  usually 
noted  for  its  chronicity,  often  remaining  stationary  for  many  years. 
I  have  repeatedly  seen  patients  forty  to  fifty  years  of  age  who 
during  childhood  had  suffered  from  enlarged  cervical  glands,  which 
eventually  diminished  in  size,  but  did  not  disappear,  which,  after 
years,  again  became  the  seat  of  an  active  tubercular  process.  In 
exceptional  cases  this  affection  pursues  an  acute  course.  Delafield 
reports  an  exceedingly  interesting  case  of  this  kind  (Medical  Record, 
vol.  i.  p.  425, 1885).  The  disease  commenced  with  an  enlargement 
of  one  of  the  cervical  glands  near  the  angle  of  the  lower  jaw  with 
a  temperature  of  40°  C.  (104°  F.)  and  rapid  extension  to  the 
proximal  glands  as  far  as  the  clavicle.  Symptoms  of  pulmonary 
complication  were  not  present.  Rapid  emaciation  and  marked 
anaemia  supervened,  followed  after  six  weeks  by  swelling  of  axillary 
and  inguinal  glands.  Ophthalmic  examination  revealed  the  same 
conditions  of  retina  and  papilla  as  in  leukemia  or  Bright' s  disease. 
A  few  days  after  the  beginning  of  the  disease  profuse  diarrhoea 
and  reduction  to  nearly  normal  temperature  occurred.  The  diag- 


TUBERCULOSIS    OF    THE    LYMPHATIC    GLANDS.       179 

nosis  was  between  malignant  lymphoma  and  tuberculous  adenitis. 
During  the  further  course  of  the  disease  bronchial  breathing  in 
both  lungs  appeared.  Heart,  liver,  and  spleen  appeared  to  be  nor- 
mal. Urine  normal,  but  increase  of  temperature  and  respirations 
took  place  during  this  time.  Death  occurred  in  less  than  five 
months.  At  the  autopsy  the  lungs  were  found  congested  and  oede- 
matous,  with  red  hepatization  of  the  lower  lobes,  and  a  few  miliary 
tubercles.  The  spleen  contained  many  miliary  tubercles  the  size 
of  the  head  of  a  pin,  and  most  of  them  in  a  state  of  cheesy  degen- 
eration. The  mesenteric  glands  were  much  enlarged ;  and  a  few 
of  them  in  a  condition  of  cheesy  degeneration  and  calcification.  In 
the  cheesy  masses  bacilli  were  found.  All  the  cervical  glands  were 
affected  with  softening  and  cheesy  degeneration  in  the  centre.  The 
calcification  of  mesenteric  glands  pointed  to  an  earlier  affection. 
The  disease  remained  latent  and  recurred  in  the  same  glands,  and, 
later,  extended  to  the  cervical  glands.  This  case  resembles  the 
cases  described  by  Hilton-Fagge  and  Pye-Smith.  Next  to  the  cer- 
vical glands  the  glands  of  the  axilla  are  most  frequently  affected. 
In  my  experience  the  operative  treatment  of  tuberculosis  of  the 
axillary  glands  has  yielded  more  satisfactory  results  than  when  the 
same  operation  was  made  under  similar  conditions  on  the  glands  of 
the  neck.  Tuberculosis  of  the  inguinal  glands  is  an  extremely 
rare  affection,  and  when  present  is  usually  associated  with  primary 
tuberculosis  of  the  genital  organs.  From  a  practical  standpoint 
the  following  two  papers  are  of  great  importance. 

Friinkel  ("  Zur  Histologie,  Aetiologie  und  Therapie  der  Lym- 
phomata  Colli,"  Prager  Zeitschriftf.  Jleilkunde,  1885,  Hefte  2  und 
3),  for  three  years,  made  it  his  duty  to  study  the  histological  struc- 
ture of  all  lymphatic  tumors  which  were  extirpated  in  Billroth's 
clinic.  As  the  result  of  his  observations  he  classified  all  primary 
tumors  of  the  lymphatic  glands  examined  into  two  classes :  1 . 
Lymphatic  tuberculosis;  2.  Lympho-sarcoma.  He  also  described 
a  simple  hyperplasia  of  the  glands,  which  present  under  the  micro- 
scope only  healthy  glandular  tissue.  In  the  tubercular  glands  he 
found  the  histological  structure  of  tubercle  perfect,  and  never  failed 
in  detecting  the  bacillus  of  tuberculosis.  In  persons  between  fifteen 
and  thirty  years  of  age  he  found  local  tuberculosis  of  the  lymphatic 
glands  as  a  quite  frequent  affection.  In  his  paper  he  gives  the 
clinical  histories  of  1 48  cases  of  glandular  tuberculosis.  Only  in 
15  of  this  number  were  the  lungs  affected.  In  18  the  patients  were 
weak  and  badly  nourished ;  while  in  72  the  general  health  was 
unimpaired.  The  age  of  the  patients  varied  from  nine  to  fifty-one 
years.  On  an  average  the  duration  of  the  disease  was  from  three 
to  four  years;  the  shortest  time  was  two  months,  and  the  longest 
thirty  years.  Of  special  etiological  interest  is  the  case  of  a  woman, 


180      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

fifty-one  years  of  age,  who  had  given  birth  to  two  children,  their 
father  being  the  subject  of  advanced  tuberculosis,  and  both  of 
whom  died  of  tuberculosis.  She  had  been  in  perfect  health  until 
her  forty-ninth  year,  when  she  was  attacked  simultaneously  with 
pulmonary  and  glandular  tuberculosis.  In  128  of  the  reported  cases 
the  glands  were  extirpated,  some  of  the  operations  being  quite  seri- 
ous; in  16  cases  the  internal  jugular  vein  had  to  be  tied.  In  91  of 
the  operations  the  wound  healed  by  primary  union,  and  in  25  the 
healing  was  retarded  by  suppuration.  Erysipelas  complicated  the 
result  five  times.  In  one  of  these  cases  a  large  part  of  the  tubercu- 
lous mass  was  left,  and  it  was  noticed  that  the  erysipelas  had  no 
effect  on  the  tubercular  process.  Only  in  49  of  the  cases  operated 
on  could  the  final  result  be  obtained.  Taking  three  and  a  half 
years  as  the  time  when  the  patient  could  be  considered  exempt  from 
a  recurrence  of  the  disease,  it  was  ascertained  that  in  24  per  cent, 
no  relapse  followed  the  operation  ;  a  local  relapse  was  observed  in 
14  per  cent.,  and  reappearance  of  the  disease  distant  from  the  seat 
of  operation  in  4  per  cent. 

As  lymphatic  tuberculosis,  in  most  instances,  signifies  the  entrance 
of  bacilli  through  a  loss  of  continuity  of  the  skin  or  of  the  mucous 
membrane,  or  through  the  socket  of  a  carious  tooth,  localization 
occurring  in  one  of  the  nearest  glands  to  the  portio  invasionis,  it 
must  be  looked  upon  as  a  local  process,  and  amenable  to  timely 
surgical  treatment  by  the  removal  of  all  of  the  infected  tissues. 
The  capsule  of  the  lymphatic  glands  furnishes  an  efficient  barrier 
against  infection  of  the  para-glandular  tissue  for  a  long  time,  and 
perforation  only  takes  place  after  the  disease  has  made  considerable 
progress,  and  has  been  followed  by  extensive  caseation,  and  espe- 
cially by  suppuration.  Early  operations  are  as  necessary  in  the 
treatment  of  tubercular  adenitis  as  in  the  treatment  of  malignant 
tumors,  and  holds  out  more  encouragement  so  far  as  a  permanent 
cure  is  concerned.  By  a  thorough  removal  of  the  primary  focus 
of  infection,  successive  infiltration  of  proximal  glands  and  miliary 
tuberculosis  are  prevented  almost  to  a  certainty  if  the  operation  is 
performed  before  the  para-glandular  tissues  are  affected.  If  the 
operation  is  done  at  such  a  favorable  time,  it  is  not  attended  by  any 
great  difficulties,  as  the  glands  can  be  readily  enucleated,  and  as 
suppuration  has  not  taken  place  the  wound  usually  heals  by  primary 
union.  If,  however,  the  tubercular  inflammation  has  involved 
many  glands,  and  has  extended  to  the  connective  tissue  surround- 
ing the  glands,  the  operation  becomes  one  of  the  most  formidable 
in  surgery  on  account  of  the  close  proximity  of  important  vessels 
which  are  often  imbedded  in  the  mass.  Under  such  circumstances 
a  complete  removal  is  often  impossible  and  early  local  recidivation 
is  inevitable,  owing  to  imperfect  removal  of  the  infected  area. 


•  PLATE    VII  I. 


From  encysted  bronchial  gland  in  miliary  tuberculosis.     Giant  cell 
with  radiating  arrangement  of  bacilli.     (Koch.)     700  diam. 


TUBEKCULOSIS  OF  THE  BONES.          181 

Traumatic  dissemination  is  very  likely  to  follow  all  imperfect 
operations,  in  which  portions  of  glands  or  infected  capsules  are  left 
behind  by  inoculation  of  the  surface  of  the  wound  with  the  bacilli. 
I  have  seen  in  a  number  of  such  cases  as  early  as  a  week  after  the 
operation  the  entire  wound  surface  covered  by  a  thick  layer  of 
granulation  tissue,  which  showed  all  the  histological  evidences  and 
possessed  all  the  bacteriological  properties  of  tubercular  tissue.  As 
an  additional  testimony  in  favor  of  the  operative  treatment  of 
tubercular  glands,  I  will  quote  from  the  paper  of  Schnell  ( Ueber 
Erfolge  von  Extirpation  tuberculoser  Lymphome,  Dissertation,  Bonn, 
1885),  who  collected  56  cases  of  tuberculosis  of  the  cervical  glands, 
which  were  treated  by  extirpation  in  the  clinic  at  Bonn.  In  37  of 
these  cases  he  was  able  to  learn  the  ultimate  result.  In  57  per 
cent,  the  operation  was  followed  by  complete  recovery ;  in  27  per 
cent,  the  disease  returned  at  site  of  operation ;  and  in  four  cases 
death  resulted  from  pulmonary  tuberculosis.  The  largest  number 
of  cases  were  patients  between  ten  and  twenty  years  of  age. 

5.  Bones. 

Tuberculosis  of  the  bones  is  an  exceedingly  frequent  affection  in 
children  and  young  adults.  Its  favorite  location  is  in  the  epiphy- 
seal  extremities  of  the  long  bones,  although  it  is  also  quite  fre- 
quently met  with  in  the  short  bones  of  the  carpus  and  tarsus, 
and  some  of  the  flat  and  irregular  bones,  as  the  ribs,  scapula,  ilium, 
and  vertebrae.  Direct  infection  is  never  observed,  and  when  the 
disease  has  made  its  appearance  it  is  only  an  evidence  of  the  ex- 
istence of  tubercular  infection  at  an  earlier  day,  or  the  presence 
of  a  tubercular  process  in  some  other  organ.  We  observe  clinically 
what  Miiller  has  demonstrated  experimentally,  that  when  the  bacilli 
of  tuberculosis  are  present  in  the  blood  current,  very  often  localiza- 
tion takes  place  near  the  epiphyseal  cartilage  in  young  persons  by 
the  microbes  becoming  arrested  in  one  of  the  terminal  branches  of 
an  artery,  the  lumen  of  which  becomes  obliterated  by  the  presence 
of  an  embolus  of  granulation  tissue  containing  bacilli,  or  the  lumen 
of  the  vessel  is  gradually  diminished  by  the  formation  of  a  mural 
thrombus,  which  forms  around  bacilli  implanted  upon  the  vessel 
wall,  and  the  lumen  of  the  vessel  is  finally  completely  obstructed 
by  the  growth  of  the  thrombus.  The  new  vessels  in  the  vicinity 
of  the  centres  of  growth  in  the  bones  of  young  persons,  on  account 
of  their  imperfect  structure  and  irregular  contour,  furnish  the  most 
favorable  conditions  for  the  arrest  of  floating  granular  matter  and 
the  localization  of  pathogenic  microbes.  This  predisposing  ana- 
tomical element  goes  far  to  explain  the  frequency  with  which  we 
meet  with  tubercular  foci  in  the  epiphyseal  extremities  of  the  long 


182       CLINICAL    FORMS    OF    SURGICAL     TUBERCULOSIS. 

bones.  Before  the  age  of  puberty  it  is  safe  to  state  that  the  primary 
lesion  in  tubercular  affections  of  joints  is  located  in  one  or  both  of 
the  epiphyses  of  the  bones  which  enter  into  the  formation  of  the 
joint,  while  in  the  adult  primary  tuberculosis  of  the  syuovial  mem- 
brane is  more  frequently  met  with.  As  age  advances  and  the  pro- 
cess of  ossification  is  completed,  the  predisposing  localizing  causes 
in  bone  seem  to  disappear,  while  the  syuovial  membrane  becomes 
more  susceptible  to  primary  localization. 

Of  204  specimens  of  tuberculous  joints  examined  by  Miiller  and 
quoted  by  Konig  (Die  Tubereulose  der  Knochen  und  G-elenke,  Ber- 
lin, 1884,  p.  66),  158  were  primary  osteal  and  46  primary  synovial 
tuberculosis. 

As  soon  as  embolic  infection  in  bone  has  taken  place,  a  process 
of  decalcification  occurs  around  the  tubercular  em  bolus  or  thrombus, 
and  the  preexisting  connective  tissue  is  transformed  into  embryonal 
or  granulation  tissue  which  imparts  to  the  product  of  the  specific 
inflammation  its  characteristic  fungous  appearance.  It  is  not  often 
that  only  a  single  focus  of  tubercular  infection  in  bone  is  present ; 
more  frequently,  two  or  three  foci  appear  at  the  same  time  or  in 
slow  or  rapid  succession,  and  it  is  not  unusual  to  find  that  two 
neighboring  epiphyses  are  infected  at  the  same  time,  or  during  the 
course  of  the  disease.  The  granulation  tissue  in  bone  undergoes 
the  same  secondary  degenerative  tissue-changes  as  in  the  lymphatic 
glands,  hence,  in  advanced  cases  we  expect  to  meet  with  caseation, 
liquefaction  of  the  caseous  material,  and  suppuration  in  cases  of 
secondary  infection  with  pyogenic  microbes.  The  obstruction  of  a 
small  artery  by  an  embolus  or  thrombus  which  contains  the  bacilli 
of  tuberculosis  usually  leads  to  sequestration  of  a  triangular  piece  of 
bone  which  maps  out  the  area  of  tissue  which  received  its  blood- 
supply  from  the  obstructed  vessel;  thus  the  triangular  sequestra  are 
formed  that  are  so  frequently  met  with  in  osteal  tuberculosis  of  the 
epiphyseal  extremities.  It  is  seldom  that  tuberculosis  of  bone  de- 
velops in  the  course  of  pulmonary  tuberculosis,  but  pulmonary  and 
miliary  tuberculosis  can  often  be  traced  to  a  tuberculous  focus  in  a 
bone.  The  intimate  relations  which  exist  between  the  tubercular 
nodule  in  bone  and  the  bloodvessels  furnish  a  satisfactory  explana- 
tion of  the  frequency  with  which  systemic  infection  takes  place.  As 
soon  as  the  granulation  process  reaches  an  adjacent  vein,  the  tissues 
of  the  vein-wall  undergo  the  same  process,  and  the  bacilli  reach  the 
lumen  of  the  vessel  and  reenter  the  systemic  circulation,  and  give 
rise  to  miliary  tuberculosis  in  organs  which  are  anatomically  pre- 
disposed to  localization.  As  long  as  the  decalcification  of  the  sur- 
rounding bone  goes  on,  the  infection  is  progressive ;  but  as  soon  as 
sclerosis  takes  place  the  process  becomes  limited,  as  the  microorgan- 
isms are  shut  in,  as  it  were,  by  an  impermeable  wall  of  sclerosed 


TUBEKCULOSIS    OF    THE    BONES.  183 

bone.  The  most  unfavorable  conditions  are  created  in  cases  in 
which  the  tubercular  focus  becomes  the  seat  of  a  secondary  infec- 
tion with  pyogenic  microbes,  as  the  suppurative  process  opens  up  to 
the  bacillus  of  tuberculosis  new  areas  for  infection  in  which  the 
resistance  of  the  tissues  to  tubercular  infection  has  already  been 
greatly  diminished.  It  is  also  during  the  suppurative  stage  that 
joint  complications  are  most  likely  to  arise.  The  clinical  history 
of  cases  of  tuberculosis  of  bone,  as  well  as  the  macroscopical  and 
microscopical  appearances  of  the  lesion,  are  typical  of  tuberculosis 
as  found  in  other  organs.  The  crucial  test  which  proves  the  tuber- 
cular character  of  most  of  the  chronic  inflammatory  affections  of 
bone  in  children  has  been  furnished  by  bacteriological  investiga- 
tions. Most  of  the  investigators  who  have  studied  the  subject 
agree  that  in  tubercular  bone  affections  it  is  sometimes  very  diffi- 
cult to  find  the  bacillus,  that  it  is  not  found  in  great  abundance, 
and  that  sometimes  it  has  evaded  even  the  most  careful  search. 

Schuchardt  and  Krause  ("  Ueber  das  Vorkommen  der  Tuberkel- 
bacillen  bei  fungosen  und  scrophulosen  Entziindungen,"  Fortschritte 
der  Meditin,  B.  i.  No.  2,  p.  277)  examined  a  great  variety  of  tuber- 
cular lesions  and  came  to  the  conclusion  that  tubercle  bacilli  are 
present  without  exception,  but,  as  a  rule,  few  in  number,  and  only 
to  be  found  after  long  and  patient  search.  They  found  them 
invariably  present  in  cases  of  secondary  and  primary  tuberculosis 
of  synovial  membranes,  tuberculosis  of  bone,  in  tubercular  abscesses, 
and  in  the  latter  cases  not  in  the  pus,  but  in  the  granulations  of  the 
abscess- wall. 

Renken  (Jahrbuchf.  Kinderheilkunde,  B.  xxv.)  found  the  bacillus 
of  tuberculosis  in  all  cases  of  spina  ventosa  which  he  examined. 

Miiller  ("  Ueber  den  Befund  von  Tuberkel-bacillen  bei  fungosen 
Knochen  und  Gelenk  affection  en,"  Centralblatt  /.  Chirurgie,  1884, 
No.  3)  studied  carefully  numerous  specimens  of  synovial  and  bone 
tuberculosis  with  special  reference  to  the  existence  of  the  bacillus 
of  tuberculosis,  and  although  the  results  in  a  number  of  cases  were 
negative,  he  believes  that  the  most  intimate  and  direct  etiological 
relations  exist  between  the  bacillus  and  all  tubercular  lesions  ir» 
bones  and  joints.  Among  others  who  have  shown  the  never-failing 
presence  of  the  bacillus  of  tuberculosis  in  different  forms  of  surgi- 
cal tuberculosis,  including  bones  and  joints,  may  be  mentioned 
Kanzler  (u  Ueber  das  Vorkommen  des  Tuberkel -bacillus  in  scro- 
phulosen Localerkrankungen,"  Berl.  klin.  Woehenschrift,  1884,  pp. 
23-41),  Mogling  (Ueber  chirurgische  Tuberculosen,  Dissertation, 
Tubingen,  1884),  Bouilly  ("  Note  sur  la  presence  des  bacilles  dans 
les  lesions  chirurgicales  tuberculeuses,"  Revue  de  Ghirurgie,  1883, 
No.  11),  and  Letulle  (G-az.  hebd.  de  Med.  et  Chir.,  1884,  49,  51, 
52).  Kanzler  wished  to  make  a  distinction  between  scrofulous 


184      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

affections  and  tuberculosis,  as  he  found  the  bacilli  not  as  constant 
in  the  former,  and  observed  that  after  implantation  of  tissue  of 
scrofulous  affections  in  animals,  the  process  was  slower  than  after 
inoculation  with  tubercular  products.  Letulle  considers  scrofula 
and  tuberculosis  as  belonging  to  one  and  the  same  disease,  of  which 
the  former  constitutes  the  milder  form,  and  appearing  externally, 
while  the  latter  represents  the  graver  form,  attacking  in  preference 
the  internal  organs.  The  points  made  by  the  last  two  authors  are 
too  unimportant  in  still  maintaining  a  scientific,  or  even  practical 
distinction  between  scrofula  and  tuberculosis.  The  surgeon  must 
recognize  every  lesion  as  tubercular  in  its  origin,  nature,  and  course 
in  which  the  bacillus  of  tuberculosis  can  be  constantly  found,  and 
from  which  successful  cultivations  can  be  made,  and  with  which 
'the  disease  in  animals  can  be  produced  by  inoculation. 

7.  Joints. 

Tuberculosis  of  joints  is  so  closely  related  to  the  same  disease  in 
bone,  that  it  often  follows  the  latter,  and  when  it  occurs  as  a  pri- 
mary lesion  it  not  seldom  extends  to  the  subjacent  bone.  As 
stated  above,  it  occurs  more  frequently  as  a  primary  lesion  in  the 
adult  than  in  children.  Primary  infection  is  only  possible  through 
a  wound  of  a  joint,  as  in  the  case  referred  to  under  the  head  of 
inoculation-tuberculosis.  Tubercular  infection  of  an  intact  joint 
presupposes  the  entrance  of  the  bacillus  of  tuberculosis  through 
some  infection-atrium  into  the  systemic  circulation,  or,  the  diffu- 
sion of  bacilli  through  the  same  channel  from  some  preexisting 
tubercular  focus,  and  the  localization  of  floating  bacilli  in  the 
synovial  membrane  by  capillary  embolism,  or  mural  implantation. 
A  single  tubercular  nodule  on  the  surface  of  the  synovial  mem- 
brane may  lead  in  a  comparatively  short  time  to  diffuse  tubercu- 
losis over  the  entire  surface  of  the  membrane  by  local  diffusion  of 
the  microbe,  in  which  the  movements  of  the  joint  play  an  impor- 
tant part.  When  the  synovial  surface  has  become  the  seat  of  diffuse 
tuberculosis,  the  tissues  undergo  the  same  pathological  changes  as 
during  the  first  stage  of  tuberculosis  in  other  organs,  and  it  is  the 
characteristic  granulation  tissue  which  has  given  to  this  form  of 
arthritis  the  name  of  fungous  synovitis  and  synovitis  hyperplastica 
granulosa.  During  the  early  stages  of  the  disease  the  surgeon  meets 
with  two  distinct  classes;  in  one  the  tubercular  infection  produces 
a  pulpous  condition  of  the  entire  synovial  sac,  with  little  or  no  effu- 
sion into  the  joint,  the  swelling  being  due  entirely  to  the  presence  of 
a  thick  layer  of  granulation  tissue,  the  true  tumor  albus  of  the  older 
writers.  This  form  of  tuberculosis  gives  rise  at  an  early  stage  to 
extensive  deformity  of  the  joint,  flexion,  rotation,  and,  in  the  case 


TUBERCULOSIS    OF    THE    JOINTS.  185 

of  the  knee-joint,  partial  dislocation  of  the  tibia  backward.  lu  the 
other  variety,  the  fungous  granulations  are  less  marked,  but  a 
copious  effusion  into  the  knee-joint  takes  place,  which  simulates  a 
catarrhal  synovitis  until  time  and  the  effect  of  treatment  enable 
the  surgeon  to  make  a  correct  differential  diagnosis.  In  this  form 
Konig  assures  us  that  he  has  never  observed  a  tendency  to  flexion, 
or  any  other  form  of  displacement  of  the  joint  surfaces.  If  sup- 
puration takes  place,  which  is  not  very  often  the  case,  it  begins  in 
the  granulations  which  cover  the  synovial  membrane,  and  the  pus 
accumulates  in  the  cavity  of  the  joint  until  perforation  of  the  cap- 
sule takes  place.  During  the  suppurative  process,  the  superficial 
granulations  are  destroyed,  and  the  tubercular  infection  penetrates 
deeper,  and  as,  during  the  destructive  process,  bloodvessels  are 
destroyed  the  patient  is  exposed  to  the  additional  risks  of  general 
infection.  If  such  a  joint  opens  spontaneously,  or  is  not  incised 
under  the  strictest  antiseptic  precautions,  the  additional  infection 
from  without  leads  to  the  most  serious  consequences,  as  under  these 
circumstances  the  pus-microbes  are  brought  in  contact  with  a  surface 
which  has  been  admirably  prepared  for  suppurative  and  septic 
processes  by  the  antecedent  pathological  changes. 

Tuberculosis  of  a  joint  may  terminate  in  a  spontaneous  cure  in 
cases  in  which  the  intensity  of  the  infection  is  slight,  or  the  resist- 
ance on  the  part  of  the  patient  is  so  great  that  the  fungous  granu- 
lations do  not  undergo  degenerative  changes,  but  are  converted  into 
connective  tissue.  A  partial  or  complete  synechia  of  the  joint  is 
often  one  of  the  unavoidable  results  in  such  cases.  This  endeavor 
on  the  part  of  the  organism  to  limit  extension  of  the  disease  is 
often  observed  in  cases  in  which  the  joint  affection  occurs  in  con- 
nection with  osteal  tuberculosis.  As  soon  as  the  joint  is  perforated 
a  wall  of  granulation  tissue  is  thrown  out  around  the  seat  of  infec- 
tion, and  under  favorable  circumstances  a  partition  of  cicatricial 
tissue  is  formed,  which  isolates  the  infected  from  the  intact  portion 
of  the  joint.  In  such  instances  we  have  an  illustration  how  the 
tubercular  process  is  retarded,  and  sometimes  permanently  arrested 
by  the  transformation  of  granulation  into  connective  tissue.  For 
such  a  favorable  termination  to  take  place  it  is  necessary  that  the 
tubercular  virus  should  become  attenuated  by  age,  or  want  of  a 
proper  nutrient  medium,  or  that  the  pathogenic  effect  of  the  bacilli 
should  be  neutralized  by  an  adequate  resistance  on  the  part  of  the 
tissues  before  degenerative  changes  have  occurred  in  the  granulation 
tissue.  An  exceedingly  practical  observation  has  been  recently 
made  by  a  number  of  surgeons  in  reference  to  the  influence  of 
operative  interference  in  tuberculous  joints  in  the  dissemination  of 
the  disease.  Kouig  observed  in  his  own  practice  sixteen  cases  of 
miliary  tuberculosis  following  shortly  after  resection  of  tuberculous 


186      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

joints,  and  he  believes  that  the  generalization  of  the  process  was 
favored,  if  not  directly  produced,  by  the  operation.  It  is  not  diffi- 
cult to  conceive  the  modus  operandi  of  such  an  occurrence.  The 
resection  wound  opens  numerous  veins  in  the  bone,  the  lumina  of 
which  remain  patent  ready  for  the  introduction  of  minute  frag- 
ments of  granulation  tissue  or  bacilli,  which,  on  entering  the  venous 
circulation,  are  the  direct  cause  of  metastatic  tuberculosis  in  distant 
organs. 

Wartraann  (Deutsche  Zeitschrift  f.  Chirurgie,  B.  xxiv.  Hefte  5,  6), 
after  giving  a  careful  account  of  the  results  following  excision  of 
tuberculous  joints  in  the  hospital  practice  of  Feurer,  has  collected 
from  the  practice  of  different  operators  837  cases  of  excisions  for 
tuberculosis.  Of  this  number,  225  died.  Of  the  fatal  cases,  in 
26  death  followed  the  operation  closely,  and  resulted  from  acute 
tuberculosis,  probably  induced  by  the  operation.  In  these  cases  we 
must  take  it  for  granted  that  a  tubercular  focus  during  the  opera- 
tion furnished  the  essential  fragments  of  granulation  tissue,  or  free 
bacilli  which  were  aspirated,  or  forced  into  the  openings  of  wounded 
vessels,  and  through  them  into  the  general  circulation.  That  fungous 
synovitis  is  a  genuine  tuberculosis  has  been  abundantly  illustrated 
by  clinical  experience,  microscopical  examinations,  and  particularly 
the  results  obtained  by  implantation  experiments  in  animals.  I 
will  only  refer  to  the  work  of  Tavel  (Senn  :  Four  Months  among 
the  Surgeons  of  Europe,  1887,  Chicago,  p.  154)  in  this  connection, 
who  has  been  studying  in  a  systematic  manner  the  diagnostic  value 
of  implantation  of  tubercular  material  in  animals,  mainly  guinea- 
pigs.  Granulation  tissue  from  tubercular  joints  in  his  experiments 
on  guinea-pigs  invariably  produced  acute,  diffuse  tuberculosis,  and 
death  in  from  five  to  six  weeks.  The  course  of  the  disease  in  the 
animal  is  typical ;  at  the  point  of  inoculation  a  hard  nodule  appears 
first,  the  result  of  a  traumatic  inflammation  of  the  tissues  around 
the  graft.  Next  a  lymphatic  gland  becomes  enlarged  in  the  imme- 
diate vicinity  of  the .  primary  seat  of  infection,  which  is  always 
done  in  the  flank,  consequently  the  inguinal  glands  enlarge  first. 
Glandular  infection  increases  rapidly  ;  after  the  whole  chain  of 
lymphatic  glands  in  the  groin  are  involved,  the  axillary  glands 
become  affected.  At  the  post-mortem  examination  it  was  always 
found  that  of  the  internal  organs  the  spleen  becomes  affected  first, 
then  the  liver  and  lungs,  but  usually  the  disease  is  so  diffuse  that 
scarcely  an  organ  remains  exempt.  When  the  diagnosis  between 
syphilis  and  tuberculosis  cannot  be  made,  either  clinically,  or  by  aid 
of  the  microscope,  inoculation  experiments  always  give  positive  and 
reliable  information.  When  the  lesion  is  tubercular  the  animal 
always  becomes  tubercular  and  dies.  When  it  is  syphilitic,  the 
inoculation  is  harmless,  and  the  animal  remains  well.  So  far,  only 


TUBEKCULOSIS    OF    THE    TENDON-SHEATHS.        187 

one  animal  that  was  inoculated  with  tuberculous  material  lias  lived 
for  five  months,  and  in  this  case  a  large  abscess  formed  at  the  point 
of  inoculation  a  few  weeks  after  the  operation.  Examination  of 
the  contents  of  the  abscess  showed  abundant  bacilli  of  tuberculosis ; 
a  gland  in  the  groin  remains  enlarged,  and  the  disease,  if  not 
arrested  by  the  suppurative  inflammation,  may  have  become  latent. 

7.   Tendon-sheaths. 

Tuberculosis  of  the  tendon-sheaths,  or,  as  Hueter  terms  it,  tendo- 
vaginatis  granulosa,  has  only  recently  been  recognized  and  described 
as  an  independent  primary  lesion.  Hueter,  in  his  most  admirable 
text-book  on  surgery  (G-rundriss  der  Chirurgie,  B.  i.  S.  127),  says 
that  this  affection  is  seldom  met  with  as  a  primary  lesion,  but  that 
it  appears  usually  as  a  complication  of  joint  tuberculosis.  Volk- 
mauu,  in  his  classical  article  on  diseases  of  joints  ("Die  Krank- 
heiten  der  Bewegungsorgaue,"  Pitha  u.  Billroth,  B.  xi.  S.  866), 
devotes  only  a  few  sentences  to  this  part  of  his  subject.  The  first 
scientific  treatise  on  this  affection  came  from  the  clinic  at  Gottingen 
by  Riedel.  Another  important  paper  on  the  same  subject  was 
published  by  Beger  ("  Die  Tuberculose  der  Sehnenscheiden," 
Deutsche  Zeitschrift  f.  Chirurgie,  B.  xxi.  S.  385),  who  reports  four 
cases  that  occurred  in  the  clinic  at  Leipzig. 

The  chronic  tendo-synovitis,  or  compound  ganglion  of  the  older 
text-books,  has  been  shown  to  be,  on  careful  clinical  observation, 
microscopical  examination,  and  bacteriological  research,  cases  of 
local  tuberculosis.  The  extension  of  tubercular  processes  along 
tendon-sheaths  from  a  tuberculous  joint  after  perforation  has,  for  a 
long  time,  been  known  to  occur,  but  as  a  primary  lesion  it  has 
only  been  recently  introduced  into  surgical  nomenclature.  When 
this  affection  occurs  primarily  and  independently  of  tuberculosis  of 
an  adjacent  joint,  infection  with  the  bacillus  of  tuberculosis  takes 
place  by  localization  of  floating  microbes  in  some  small  vessel,  and 
subsequently  the  pathological  processes  in  the  tendon- sheaths 
resemble  those  of  tuberculous  joints.  In  some  cases  the  products 
of  the  disease  are  massive  granulations  which  occupy  the  inner 
surface  of  the  tendon-sheath,  in  others  the  fungosity  is  less,  but  a 
copious  synovial  exudation  is  thrown  out,  while  in  a  third  class  the 
granulations  form  hard  white  masses,  the  so-called  corpora  ory- 
zoidea.  The  intrinsic  tendency  of  the  disease  consists  in  progressive 
extension  by  continuity  of  structure  along  the  tendon  primarily 
affected,  and  when  this  tendon  is  part  of  a  compound  tendon  the 
disease  gradually  creeps  from  tendon  to  tendon  until  all  of  the 
sheaths  are  involved.  As  this  affection  is  met  with  most  frequently 
in  the  tendon-sheaths  surrounding  the  carpus,  and  as  these  sheaths 


188      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

are  not  infrequently  in  direct  communication  with  the  wrist-joint 
by  means  of  small  synovial  sacs,  it  extends  to  the  joint  by  con- 
tinuity of  surface. 

Konig  ("  Die  Bedeutuug  des  Faserstoffes  fur  die  pathologisch- 
anatomische  und  die  klinische  Eutwicklung  der  Geleuk  und  Seh- 
nenscheiden-Tuberculose,"  Centralblatt  f.  d.  gesammte  Med.,  1886, 
No.  25)  assigns  to  the  bacillus  of  tuberculosis  properties  which  place 
it  among  the  agents  which  produce  fibrinous  inflammation.  The 
rice  bodies  in  the  tendon-sheaths  the  seat  of  a  chronic  inflammation 
he  considers  as  the  product  of  a  fibrinous  inflammation  caused  by 
the  presence  of  the  bacillus  of  tuberculosis.  Nicaise,  Poulet,  and 
Villard  (Nature  tuberculeuse  des  hygromes  et  des  synovites  tendi- 
neuses  a  graim  riziformes,  1884)  examined  four  cases  of  hygroma 
containing  rice  bodies,  and  found  in  all  of  them  the  bacillus  of 
tuberculosis.  I  have  observed  this  form  of  inflammation  of  the 
tendon-sheaths  in  the  common  extensors  and  flexors  of  the  hand, 
the  peroneus  longus,  the  tendon  of  the  patella,  and  the  tendo- 
Achillis.  One  of  these  cases  was  remarkable  for  its  acuity. 
The  patient  was  a  man  sixty  years  of  age,  laborer,  and  addicted  to 
intemperance.  About  the  beginning  of  the  year  I  examined  him 
at  the  request  of  another  physician,  and  found  an  oblong  swelling 
on  the  dorsum  of  the  hand  corresponding  to  the  extensor  tendon  of 
the  index  finger.  The  swelling  was  not  painful,  and  but  little 
tender  on  pressure.  Fluctuation  was  well  marked ;  on  deep 
pressure  movable  bodies  could  be  distinctly  felt  which  were  recog- 
nized as  corpora  oryzoidea.  An  operation  was  advised,  but  was 
declined.  A  few  weeks  ago  the  patient  was  admitted  into  the 
Milwaukee  Hospital,  being  completely  incapacitated  from  following 
his  occupation.  At  this  time  the  dorsum  of  the  hand  corresponding 
to  the  index  and  middle  fingers,  and  the  radial  aspect  of  the  fore- 
arm as  far  as  the  middle,  presented  a  continuous  swelling  with 
well-marked  fluctuation.  The  swelling  had  become  painful,  and 
exceedingly  tender  on  pressure.  Under  strict  antiseptic  precau- 
tions the  swelling  was  incised  in  its  entire  length,  and  a  large 
quantity  of  synovia-like  fluid  and  softened  rice  bodies  escaped. 
The  sheath  of  the  extensor  commuuis  digitorum  and  extensors  of 
the  wrist  were  lined  with  a  thick  layer  of  fungous  granulations, 
and  near  the  annular  ligament  numerous  loose  attached  rice  bodies 
were  found.  The  tendon-sheaths  were  carefully  dissected  out,  and 
the  whole  wound,  after  thorough  disinfection,  dusted  with  iodoform, 
drained  and  sutured.  A  copious  antiseptic  dressing  of  iodoform 
gauze  and  sublimated  moss  was  applied,  and  the  forearm  and  hand 
fixed  upon  an  anterior  splint.  Inoculations  of  the  fluid  from  the 
sheath  upon  potato  remained  sterile.  Cultivation  upon  solidified 
serum,  obtained  from  a  hydrocele,  showed,  after  a  few  weeks,  a 


TUBERCULOSIS    OF    THE    PERITONEUM.  189 

scanty  culture  of  the  bacillus  of  tuberculosis.  Implantation  of  one 
of  the  rice  bodies  into  the  subcutaneous  connective  tissue  of  a 
guinea-pig  resulted  in  a  typical  tuberculosis,  starting  from  the 
point  of  inoculation,  spreading  to  adjacent  lymphatic  glands,  and 
finally  resulting  in  miliary  tuberculosis. 

8.  Peritoneum. 

Primary  tuberculosis  of  the  peritoneum  has  recently  been  de- 
scribed as  a  local  tuberculosis  amenable  in  some  cases,  at  least,  to 
operative  treatment.  Localization  of  the  bacillus  takes  place  in 
accordance  with  the  form  of  tuberculosis,  of  which  three  distinct 
varieties  are  recognized  by  pathologists  and  clinicians  : 

a.  As  a  part  of  a  general  diffuse  tuberculosis ; 

b.  Extension  of  an  adjacent  tubercular  process  to   the   perito- 
neum ;  and 

c    As  a  primary  tuberculosis. 

For  the  surgeon,  only  those  cases  have  interest  which  are  classi- 
fied under  the  second  and  third  varieties.  The  prevalence  of  the 
affection  in  the  female  sex  among  the  cases  which  have  been 
reported,  points  to  the  Fallopian  tubes  as  the  primary  seat  of  infec- 
tion with  secondary  invasion  of  the  peritoneum  from  this  source. 
Although  the  genital  organs  in  the  male  are  more  frequently  the 
seat  of  tuberculosis  than  in  the  female,  so  far  only  two  cases  of 
peritoneal  tuberculosis  in  males  have  been  reported,  one  by  Kiim- 
mell  and  the  other  by  Lindfors.  Tuberculosis  of  the  peritoneum 
by  extension  from  a  tuberculous  focus  in  the  genital  organs  can 
only  mean  an  infection  by  contact,  the  bacillus  of  tuberculosis 
transferred  from  the  primary  seat  of  infection,  and  localization  by 
implantation  upon  the  peritoneal  surface.  Implantation  experi- 
ments in  animals  furnish  a  good  illustration  of  the  manner  in  which 
the  process  becomes  diffuse.  At  the  point  of  implantation  a  granu- 
lation mass  forms  around  the  graft,  and  from  here  innumerable 
tubercle  nodules  take  their  starting-point,  forming  everywhere 
granulation-tissue,  in  which  the  bacillus  may  have  found  a  new 
habitat.  The  movements  of  the  abdominal  walls  and  the  peristal- 
tic action  of  the  intestines  are  potent  factors  concerned  in  the  local 
dissemination  of  the  tubercular  infection.  In  primary  tuberculosis 
of  the  peritoneum  the  infection  takes  place  in  the  same  manner  as 
in  intact  joints,  by  floating  bacilli  becoming  arrested  in  the  capillary 
vessels  of  the  membrane  where  the  primary  nodule  forms,  from 
which  again,  as  from  a  graft,  dissemination  takes  place.  These 
cases  are,  in  the  true  sense  of  the  word,  not  cases  of  primary  tuber- 
culosis, as  the  peritoneal  affection  is  only  a  local  expression  of  an 
antecedent  infection.  In  peritoneal  tuberculosis  we  observe  the 


190      CLINICAL    FORMS    OF    SURGICAL     TUBERCULOSIS. 

same  tendency  to  limitation  of  the  infective  process  as  in  joints,  by 
the  formation  of  an  impenetrable  wall  of  connective  tissue,  which 
imparts  so  often  to  this  form  of  peritonitis  its  circumscribed  char- 
acter. 

Kiimmell  ("  Ueber  Laparotomie  bei  Bauchfelltuberculose,"  Ver- 
handl.  der  Deutschen  Gresettschaft  f.  Chirurgie,  1887,  p.  323)  looks 
upon  this  form  of  peritoneal  turberculosis  as  a  purely  local  affection 
amenable  to  surgical  treatment  in  the  same  sense  as  a  tuberculosis 
of  joints.  That  some  of  these  cases  can  be  permanently  cured  by 
local  treatment  is  well  shown  by  a  case  treated  by  Sir  Spencer 
Wells  twenty-six  years  ago  by  abdominal  section,  the  patient  hav- 
ing remained  up  to  this  time  in  perfect  health. 

In  a  recent  paper  on  this  subject  Fettling  ("  Beitrage  zur  Lapa- 
rotomie bei  Peritonealtuberculose,"  Correspondenzblatt  /.  Schweizer 
drzte,  1 887)  reports  four  cases  of  his  own,  and  gives  an  account  of 
all  the  operations  which  have  been  done  up  to  that  time,  21  in 
number.  Of  this  number,  15  recovered,  and  the  patients  are  known 
to  have  been  well  from  1  year  to  23  years,  and  in  a  number  of  cases 
their  condition  was  learned  4  to  5  years  after  the  operation.  6  of  the 
patients  died ;  2  of  sepsis,  1  of  pyaemia  several  months  after  the  opera- 
tion, and  3  of  the  continuance  of  the  disease  for  which  the  operation 
was  done.  In  5  of  the  cases  ascites  attended  the  tuberculosis,  and 
in  3  the  swelling  was  not  due  to  effusion  but  to  adhesions  between 
the  intestinal  loops,  which  were  covered  with  miliary  nodules. 

Of  fifty- four  cases  of  laparotomy  (Medical  News,  July  J4,  1888) 
in  tubercular  patients,  collected  by  Trzebicky,  four  died  from  the 
immediate  consequences  of  the  operation,  while  in  a  fifth,  death 
occurred  after  the  operation  from  acute  tuberculosis,  though  the 
fluid  had  not  re-accumulated.  One  case  died  in  four  months  of 
general  tuberculosis  without  the  peritonitis  disappearing ;  cures 
resulted  in  forty  cases,  though  here  and  there  evidence  of  pulmo- 
nary tuberculosis  was  reported.  The  majority  of  cases  were  females, 
which  may  find  its  explanation  in  the  fact  that  most  were  operated 
upon  under  an  error  in  the  diagnosis  of  ovarian  cyst.  The  statistics 
are  yet  too  meagre,  the  correctness  of  diagnosis  not  entirely  above 
doubt,  and  the  period  of  observation  after  operation  not  long 
enough;  but,  in  view  of  the  results,  there  is  no  longer  any  justifica- 
tion for  expectant  treatment.  Even  though  in  some  cases  recovery 
was  not  permanent,  the  fluid  did  not  re-accumulate,  and  the  patients 
were  relieved  of  their  distress.  Spontaneous  recovery  from  tuber- 
cular peritonitis  is  exceptional,  and  operative  interference  is  indi- 
cated the  more,  as  it  would  seem  that,  in  many  cases,  tuberculosis 
of  the  peritoneum  is  a  primary  affection,  and  the  source  of  general 
infection. 

As  all  other  therapeutical  measures  are  futile  in  such  cases,  and 


TUBEKCULOSIS    OF    THE    MOUTH.  191 

laparotomy  under  antiseptic  principles  may  be  considered  free  from 
danger,  the  operation  is  certainly  indicated.  It  consists  in  a  free 
incision,  thorough  evacuation  of  the  fluid,  and  free  drainage. 

Lindfors,  in  a  monograph  on  this  subject  ( Centralblatt  f.  Gynd- 
kologie,  February  15,  1890),  analyzes  109  recorded  cases,  which 
he  divides  into  seven  classes.  The  acute  variety  may  assume  the 
form  of  circumscribed,  general,  or  suppurative  peritonitis ;  in  the 
chronic  there  may  be  a  free  or  an  encysted  effusion,  there  may  be 
simple  adhesions,  or  the  intestines  may  be  so  adherent  as  to  cause 
intestinal  obstruction.  Lindfors  thinks  that  the  presence  of  acute 
or  chronic  pleurisy  has  an  important  bearing  on  the  diagnosis  of 
tubercular  peritonitis.  He  is  strongly  in  favor  of  laparotomy  and 
the  free  use  of  iodoform  within  the  cavity. 

The  most  recent  and  comprehensive  work  on  tuberculosis  of  the 
peritoneum,  which  has  just  appeared  from  the  pen  of  Vierordt 
("  Ueber  die  Tuberculose  der  serosen  Haute,"  Zeitschrift  f.  klin. 
Medicin,  B.  xiii.  Heft  2),  should  be  consulted  by  those  who  wish  to 
secure  for  reference  an  exhaustive  treatise  on  this  subject. 

9.  Mouth. 

We  have  now  every  reason  to  believe  that  many  cases  of  ulcer- 
ation  of  the  tongue  and  cavity  of  the  mouth  which  have  been 
heretofore  diagnosticated  and  treated  as  carcinoma,  were  not  car- 
cinoma, but  tuberculosis.  The  recent  advances  made  in  the  micro- 
scopical, bacteriological,  and  experimental  methods  of  examination 
have  succeeded  in  separating  from  syphilitic  affections  and  malig- 
nant disease  of  the  mouth  a  number  of  cases  which  belong  to  the 
long  list  of  affections  which  are  now  classified  under  the  head  of 
surgical  tuberculosis.  The  cavity  of  the  mouth  is  exposed  to  direct 
infection  with  microorganisms  which  might  be  obtained  in  the 
air  we  breathe,  the  food  we  eat,  and  the  water  we  drink.  Kemem- 
bering  the  frequency  with  which  superficial  abrasions  and  ulcera- 
tions  occur  in  this  locality,  it  is  not  strange  that  primary  tuberculosis 
should  occasionally  develop  here.  The  tubercle  bacillus  produces 
the  same  tissue-changes  here  as  on  the  surface  of  the  skin,  the  pri- 
mary pathological  product  consisting  of  granulation  tissue  which 
undergoes  molecular  retrograde  tissue  metamorphosis  followed  by 
ulceratiou.  The  tubercular  ulcer  is  covered  by  the  products  of  coagu- 
lation-necrosis, and  is  surrounded  by  a  zone  of  infiltration,  which, 
however,  does  not  present  the  same  feeling  of  hardness  as  carcinoma. 
Schliferowitsch  ("  Ueber  Tuberculose  der  Mundhohle,"  Deutsche 
Zeitschrift  f.  Chirurgie,  B.  xxvi.  Hefte  5.  u.  6)  gives  an  exhaustive 
resume  of  the  literature  on  the  subject  to  date,  and  has  collected  all 
the  recorded  cases  in  which  the  diagnosis  of  tubercular  disease  of 


192      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

the  cavity  of  the  mouth  could  be  made  with  some  degree  of  certainty. 
The  cases  number  88,  and  include  those  of  primary  and  secondary 
tuberculosis.  From  a  careful  study  of  this  affection  he  has  come  to 
the  conclusion  that  it  occurs  seldom  in  the  very  young,  and  that  it 
attacks  most  frequently  persons  between  forty  and  fifty  years  of  age. 
The  appearance  of  the  tubercular  ulcer  is  characteristic.  If  on  the 
tongue,  it  is  found  on  the  borders  near  the  tip  of  the  organ.  It 
appears  as  an  oblong  ulcer,  with  raised,  ragged  borders  of  firm  con- 
sistence, showing  the  color  of  fresh  granulations.  The  floor  appears 
as  if  covered  by  a  pseudo-membrane ;  if  this  covering  is  removed, 
the  surface  left  easily  bleeds.  The  surface  of  the  ulcer  is  uneven, 
as  if  covered  with  papillae.  The  discharge  of  pus  is  slight,  and,  in 
many  cases,  miliary  abscesses  may  be  found  around  the  ulcer.  Pain 
is  not  as  severe  as  in  carcinoma.  Lymphatic  glands  may  become 
secondarily  infected,  but  this  is  not  often  the  case.  In  the  primary 
form  of  the  disease  the  presence  of  tubercle  bacilli  is  the  safest  cri- 
terion in  fixing  the  diagnosis. 

10.   Genital  Organs. 

Cornet  has  made  some  experiments  on  tuberculosis  of  the  genital 
organs  in  animals.  In  rubbing  a  pure  culture  of  tubercle  bacilli 
in  abrasions  of  the  penis,  he  produced  a  tubercular  lesion  of  that 
organ.  In  bitches  tuberculosis  of  the  vagina  and  uterus  could  be 
produced  by  injection  of  a  pure  culture  into  the  vagina.  The  local 
lesions  were  followed  by  general  tuberculosis. 

FEMALE. — Direct  tubercular  infection  of  the  genital  tract  in 
women  has  been  observed,  but  the  cases  so  far  reported  are  few. 
Zweigbaum  (Centralblatt  f.  Bacteriologie  und  Parasitenkunde,  B.  xi. 
S.  558)  describes  a  case  of  primary  tuberculosis  of  the  portio  vagi- 
nalis  uteri,  which,  at  the  time  of  examination,  appeared  in  the  shape 
of  an  ulcer  the  size  of  a  walnut,  with  thick,  indurated  margins,  and 
cheesy  floor.  Numerous  tubercle  bacilli  were  found  in  the  secretion 
taken  from  the  surface  of  the  ulcer.  Evidences  of  pulmonary 
tuberculosis  were  apparent  at  this  time.  After  a  few  weeks  the 
ulcer  extended  toward  the  left  vaginal  wall  and  left  labia  majora. 
A  section  of  a  fragment  of  tissue  removed  from  these  parts  on 
staining  showed  numerous  bacilli.  This  form  of  tuberculosis  is 
not  frequent,  as  the  author  could  find  only  two  cases  of  vulvo-tuber- 
culosis  in  literature,  although  genital  tuberculosis  is  quite  a  frequent 
affection.  In  the  absence  of  tubercular  lesions  of  the  vagina  and 
uterus,  it  is  doubtful,  if  infection  of  the  Fallopian  tubes  can  take 
place  by  the  entrance  of  the  bacillus  through  the  genital  tract,  and 
the  relatively  frequent  occurrence  of  the  disease  in  that  part  of  the 
genital  organs  is  only  explainable  by  attributing  it  to  auto-infection 


TUBERCULOSIS    OF    THE    GENITAL    ORGANS.         193 

in  the  same  way  as  we  have  explained  the  occurrence,  for  instance, 
of  primary  tuberculosis  of  joints  and  peritoneum.  We  can  only 
safely  assume  that  tubercular  infection  of  the  tube  often,  if  not 
always,  takes  place  upon  the  basis  of  preexisting  pathological  con- 
ditions, taking  it  for  granted  that  the  healthy  tubes  do  not  present 
favorable  conditions  for  the  localization  of  the  tubercle  bacilli.  A 
catarrhal  condition  of  the  lining  membrane  of  the  tubes,  as  in  other 
organs,  undoubtedly  acts,  in  many  instances,  as  a  predisposing  cause 
to  localization  of  preexisting  microorganisms  in  the  circulation. 

Barbier  (G-az.  M6d.,  1888,  No.  39)  believes  that  a  woman  can  be 
infected  by  a  tuberculous  man  during  coitus.  Bacilli  have  been 
demonstrated  in  the  semen,  as  well  as  in  the  discharge  attending 
tuberculous  epididymitis,  The  uterus  may  be  infected  by  extru- 
sion from  tuberculous  growth  in  the  vulva,  without  any  inter- 
mediate trace  of  infection  in  the  vagina.  The  writer  even  admits 
the  possibility  that  tubercular  infection  may  be  transmitted  by  the 
finger  of  the  attendant,  by  unclean  instruments,  or  even  through 
the  medium  of  the  air. 

Primary  Tuberculosis  of  the  Fallopian  Tube. — Kotschau  (Arehiv. 
/.  G-ynakologie,  B.  xxxi.  Heft  2)  gives  a  full  description  of  a  case 
of  primary  tuberculosis  of  the  Fallopian  tube.  The  patient  was 
forty-five  years  old,  having  a  good  family  history,  and  had  suffered 
for  a  year  with  pains  in  the  abdomen,  profuse  metrorrhagia,  and 
diverse  nervous  disturbances,  She  was  treated  for  retroflexion  ; 
and  subsequently  had  an  attack  of  pelvio- peritonitis.  Vaginal 
examination  disclosed  a  firm,  smooth  movable  tumor  as  large  as 
an  apple,  to  the  right  of  the  uterus ;  this  was  taken  for  a  malig- 
nant ovarian  growth,  and  laparotomy  was  done  for  its  removal. 
On  opening  the  abdominal  cavity  a  quantity  of  turbid,  purulent 
fluid  escaped.  The  tumor,  of  oblong  shape,  was  found  lying  appa- 
rently in  a  bed  of  pus ;  on  account  of  its  intimate  adhesions  it  could 
not  be  removed.  The  patient  died  from  shock.  The  autopsy 
showed  the  uterus  enlarged  and  retro  verted.  The  right  tube  was 
tortuous  and  generally  thickened ;  near  its  distal  end  it  was  dilated 
into  a  swelling  the  size  of  a  hen's  egg,  in  the  centre  of  which  was 
a  cavity  containing  cheesy  material.  Other  smaller  caseous  deposits 
were  found  in  the  tubal  wall  in  close  proximity  to  the  large  swell- 
ing. The  ovary  on  the  same  side  was  enlarged  and  transformed 
into  a  caseous  mass ;  the  left  tube  and  ovary  showed  similar  changes, 
though  less  extensive.  The  microscopical  examination  of  the  patho- 
logical products  confirmed  the  diagnosis  of  tuberculosis. 

Werth  (Centralblatt  /.  G-ynakologie,  July  20,  1889)  in  a  recent 
paper  on  the  subject  of  tuberculous  disease  of  the  Fallopian  tubes, 
recognizes  an  acute  and  chronic  form ;  in  the  former  both  the  mus- 
cular and  serous  coats  undergo  caseous  degeneration,  numerous 

13 


194      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

bacilli  being  found  in  the  interior  of  the  tube,  Avhile  in  the  chronic 
form  the  wall  of  the  tube  undergoes  thickening  and  infiltration 
with  new  cells,  while  its  contents  contain  only  a  few  bacilli. 
The  increase  in  size  of  the  tube  is  due  to  the  collection  of  pus  in  its 
interior,  as  well  as  to  the  hypertrophy  of  the  wall.  When  suppu- 
ration takes  place  in  the  interior  of  the  tube  the  tubercular  product 
has  become  the  seat  of  a  secondary  infection  with  pus-microbes, 
hence  the  indications  for  operative  treatment  have  become  more 
urgent. 

An  interesting  case  of  primary  tuberculosis  of  the  uterus  and 
Fallopian  tubes  is  reported  by  Lebedeff.  The  patient  was  the 
widow  of  a  man  who  had  died  of  pulmonary  tuberculosis.  An 
examination  before  the  operation  revealed  a  firm,  nodulated,  intra- 
abdominal  tumor  in  the  space  of  Douglas.  An  attempt  was  made 
to  remove  the  tumor  by  laparotomy,  but  had  to  be  abandoned  as 
the  disease  had  become  too  widely  disseminated.  Six  weeks  later 
the  patient  died  with  symptoms  of  general  tuberculosis.  At  the 
post-mortem  miliary  tuberculosis  was  found  in  the  peritoneum, 
lungs,  colon,  uterus,  and  Fallopian  tubes.  The  most  advanced 
stages  of  the  disease  were  found  in  the  uterus  and  Fallopian  tubes, 
showing  that  the  disease  had  commenced  in  these  organs.  Both 
the  Fallopian  tubes  were  dilated  and  filled  with  pus,  the  epithelium 
in  parts  being  absent.  Stained  sections  from  the  uterus  and  tubes 
showed  the  presence  of  numerous  bacilli. 

Jouin  (Bulletin  Paris  Obstet.  and  G-yn.  Soc.,  March,  1889) 
believes  that  tuberculous  endometritis  from  local  infection  is  quite 
a  common  affection.  Of  nine  cases  which  were  observed  by  him, 
it  was  due  to  sexual  contact  with  men  suffering  from  genital  tuber- 
culosis. In  two  others  the  husbands  were  tuberculous,  but  had  no 
genital  tuberculosis.  He  calls  attention  to  the  fact  that  Cornil  and 
Chantemesse  have  produced  it  in  rabbits  by  injecting  bacilli  into 
the  vagina. 

Mamma. — A  number  of  well -authenticated  cases  of  primary 
tuberculosis  of  the  mamma  have  recently  been  reported.  So  far 
as  the  infection  is  concerned,  the  breast  must  be  considered  as  an 
appendage  of  the  skin.  The  bacillus  of  tuberculosis,  from  without, 
may  effect  entrance  into  the  gland  through  the  milk-ducts,  in 
which  case  the  inflammatory  process  commences  in  the  parenchyma 
of  the  gland,  or  it  may  enter  through  a  fissure  of  the  nipple,  in 
which  case  the  process  is  primarily  interstitial.  Where  direct 
infection  from  without  can  be  excluded,  the  disease  is  the  result  of 
auto-infection,  and,  on  this  account,  the  prognosis  is  always  more 
unfavorable.  The  regional  dissemination  takes  place  along  the 
chain  of  the  axillary  lymphatic  glands.  Orthmann  ("Ueber 
Tuberculose  der  weiblichen  Brustdriise,"  etc.,  Virchow's  Archiv, 


TUBEKCULOSIS    OF.  THE    GENITAL    ORGANS.          195 

B.  c.  Heft  3)  examined  the  enlarged  lymphatic  glands  in  a  case  of 
tuberculosis  of  the  mamma,  and  found  numerous  tubercle  bacilli. 

MALE. — In  the  male  primary  tuberculosis  is  most  frequently 
observed  in  the  epididymis,  for  the  reason  that  the  vessels  in  this 
structure  are  more  tortuous  and  smaller  than  in  the  remaining 
portion  of  the  testicle,  or  the  vas  deferens.  Saltzman  states  (Cen- 
tralblatt  fur  klin.  Medicin,  1888,  No.  11)  that  these  anatomical 
conditions  are  important  factors  in  the  arrest  and  localization  of 
floating  bacilli.  That  in  cases  of  tuberculosis  of  the  testicle  we  are 
only  dealing  with  an  external  manifestation  of  an  antecedent  infec- 
tion, becomes  apparent  by  the  clinical  observation  that  not  infre- 
quently both  testicles  are  infected,  either  simultaneously  or  some 
time  apart,  showing  that  the  infection  came  from  the  same  source. 
In  other  cases  the  primary  localization  takes  place  in  the  vesiculse 
seminales,  or  in  the  structure  of  the  prostate  gland.  Tuberculosis 
of  the  genital  organs  in  the  male  furnishes  one  of  the  best  exam- 
ples of  the  typical  course  of  local  tuberculosis  of  the  testicle.  A 
small,  hard  nodule  is  first  detected  in  the  epididymis,  and  from 
this  starting-point  the  whole  structure  of  the  epididymis  is  infected, 
when  the  infection  slowly,  but  surely,  extends  along  the  vas 
deferens  to  the  vesicula3  seminales,  the  prostate  gland,  and  bladder, 
and  from  this  viscus  along  the  ureters  to  the  pelvis  of  the  kidney. 
As  a  rule,  the  disease  remains  limited  to  the  genito- urinary  organs, 
but,  in  some  instances,  metastatic  infection  takes  place,  either  from 
the  genito-urinary  organs,  or  from  the  primary  source  of  infection. 
A  gentleman  is  now  under  my  treatment  who  illustrates  a  number 
of  interesting  points  descriptive  of  the  clinical  behavior  of  genital 
tuberculosis.  He  is  thirty-five  years  of  age,  married  for  ten  years  ; 
the  marriage  has  been  childless.  He  claims  that  he  has  never  had 
syphilis  or  gonorrhoea.  Tuberculosis  is  hereditary  in  the  family. 
Nine  years  ago  he  noticed  a  small,  hard  swelling  in  the  epididymis 
of  both  testicles.  Two  years  ago  symptoms  of  cystitis  appeared 
which  were  not  much  improved  by  internal  medication,  and  irriga- 
tion of  the  bladder.  Six  months  ago  his  left  knee  became  swollen 
and  painful.  Two  months  ago  he  commenced  to  suffer  from  severe 
pain  in  the  region  of  the  left  kidney.  Temperature  at  this  time 
varied  from  100°  to  103°  F.  A  swelling  soon  formed  in  the  left 
lumbar  region,  and  four  weeks  ago  I  made  an  incision  in  the 
lumbar  region  along  the  outer  border  of  the  erector  spinse  muscles 
down  to  the  kidney  and  evacuated  a  large  quantity  of  pus. 
Through  this  incision  the  kidney  could  be  distinctly  felt,  and  by 
passing  the  finger  around  it,  it  appeared  to  be  separated  from  the 
structures  surrounding  it.  The  left  knee  presents  all  the  appear- 
ances of  advanced  tuberculosis.  Pulmonary  tuberculosis  is  not 
present.  The  disease  in  both  testicles  remains  latent,  the  testicles 


196      CLINICAL    FORMS    OF    SURGICAL    TUBERCULOSIS. 

proper  are  intact,  the  epididymis  moderately  swollen  aud  indurated, 
the  vas  deferens  on  each  side  somewhat  firmer  than  normal.  The 
disease  has  extended  from  the  epididymis  to  the  pelvis  of  the  kid- 
neys, all  of  the  intervening  organs  being  involved  in  the  tubercular 
process.  The  only  apparent  manifestation  of  general  tuberculosis 
is  presented  by  the  left  knee.  An  interesting  feature  in  this  case 
is  the  formation  of  a  paranephric  abscess  around  a  pyelo- nephritic 
kidney,  which  must  be  referred  to  a  secondary  infection  with 
pus-microbes. 

Tuberculosis  of  Urethra  and  Glaus  Penis. — Kraske  has  observed 
a  case  of  tuberculous  ulceration  of  the  urethra  extending  from  the 
membranous  portion  to  the  neck  of  the  bladder,  in  a  patient  thirty- 
three  years  of  age.  The  patient  was  treated  for  chancre.  The 
autopsy  revealed  advanced  tuberculosis  of  the  geni to-urinary  tract, 
and  pulmonary  tuberculosis.  In  another  case,  a  man,  forty-nine 
years  old,  a  tuberculous  ulceration  existed  on  the  dorsum  of  the 
glans,  the  size  of  a  cent  piece.  This  sore  was  also  mistaken  for 
primary  lesion  of  syphilis.  There  were  no  signs  of  pulmonary 
tuberculosis.  The  glans  was  amputated,  when  it  was  observed 
that  the  tuberculous  infiltration  extended  deeply  into  the  cavernous 
structure.  The  lesion  could  not  be  traced  to  genital  contact,  and 
under  the  microscope  showed  the  typical  structure  of  tuberculous 
tissue. 

Vesiculce  Seminales. — In  1829  Dalmar  described  a  chronic  inflam- 
mation of  the  seminal  vesicles,  the  description  of  which  corresponds 
closely  to  that  of  tuberculosis.  Since  then  this  affection  has  been 
described  by  Albers,  Jaye,  Naumann,  Humphrey,  and  Kocher,  and 
lately  it  has  been  studied  by  Rayer,  Cruveilhier,  and  Reclus,  as 
secondary  to  tuberculosis  of  the  lungs.  As  a  secondary  affection, 
this  trouble  is  not  only  seen  in  connection  with  tuberculosis  of  the 
lungs,  but  is  more  common  after  primary  tuberculosis  of  the  epi- 
didymis, either  as  a  continuation  of  the  cheesy  degeneration  in  the 
vas  deferens,  or  spreading  by  contiguity  of  tissue  from  the  prostate. 
Primary  tuberculosis  of  these  organs  is  extremely  rare,  and  still 
less  often  diagnosed,  and  up  to  the  present  time  no  surgical  inter- 
ference has  been  attempted. 

Ullman  (CentralblaM  f.  Chirurgie,  No.  8,  1890)  reports  a  case  of 
primary  tuberculosis  of  the  right  testicle  with  secondary  affection  of 
the  seminal  vesicles  on  both  sides,  in  a  lad  seventeen  years  of  age, 
where,  after  removal  of  the  right  testicle  he  extirpated  these  organs 
through  a  semilunar  incision  in  the  perineum.  The  general  health 
of  the  patient  improved,  but  a  small  urinary  fistula  remained,  as 
during  the  operation  the  bladder  had  been  opened.  He  is  of  the 
opinion  that  the  seminal  vesicles  should  be  removed  in  primary 
tuberculosis  of  the  testicle  or  epididymis,  when  no  suspicious  symp- 


TUBERCULAR    ABSCESS.  197 

toms  have  appeared  on  the  sound  side,  and  when  on  the  affected 
side  the  vesiculse  seminales  are  already  attacked,  also  in  cases  of 
primary  tuberculosis  of  the  seminal  vesicles.  The  impotence  fol- 
lowing the  operation  should  be  no  centra-indication,  for  in  all 
reported  cases  of  tuberculosis  of  the  seminal  vesicles,  impotence 
always  occurs  in  a  short  time,  in  fact  it  is  regarded  as  a  cardinal 
symptom  of  the  disease. 

Strumpell  ("  Beitrage  zur  Diagnostik  u.  Aetiologie  der  Tuber- 
kulose  des  mannlichen  Urogenital-apparates,"  Munch,  med. 
Wochenschrift,  B.  xxxiv.  No.  31,  1887),  after  a  careful  study  of 
four  cases  of  primary  tuberculosis  of  the  genito-uriuary  organs  in 
men,  came  to  the  conclusion  that  infection  takes  place  through 
the  urethra.  The  tubercle  bacilli,  finding  no  place  for  localization 
and  growth  in  the  urethra  and  bladder,  finally  reach  the  prostate 
gland,  or  the  epididymis,  the  whole  process  resembling  inhalation- 
tuberculosis,  in  which  the  disease  manifests  itself  not  in  the  mucous 
membrane  of  the  bronchial  tubes,  but  in  the  apices  of  the  lungs. 

11.   Tubercular  Abscess. 

The  specific  effect  of  the  bacillus  of  tuberculosis  on  the  tissues 
is  to  produce  a  chronic  inflammation  which  invariably  results  in 
the  production  of  granulation  tissue.  The  granulation  tissue  must 
be  considered  in  the  light  of  a  protective  wall  to  the  surrounding 
healthy  tissue.  The  degenerative  changes  which  take  place  in  the 
granulation  tissue  are  caused  by  local  anaemia  and  the  chemical  ac- 
tion of  the  ptomaines  of  the  tubercle  bacilli,  and  consist  in  caseation 
and  liquefaction  of  the  cheesy  material  into  a  fluid  which  has  always 
been  regarded  as  pus  until  recent  investigations  have  shown  that  it 
is  simply  the  product  of  retrograde  tissue-metamorphosis.  I  believe 
that  it  can  now  be  considered  as  a  settled  fact  that  the  bacillus  of 
tuberculosis  produces  no  suppuration,  that  its  presence  indicates  only 
a  specific  form  of  inflammation,  which  terminates  invariably  in  the 
formation  of  granulation  tissue,  and  that  when  suppuration  occurs 
secondary  infection  with  pus-microbes  has  taken  place.  A  tuber- 
cular abscess,  without  the  presence  of  pus-microbes,  does  not  con- 
tain pus,  but  the  products  of  degenerative  changes  in  the  fungous 
granulations.  If  the  bacillus  meets  with  sufficient  resistance  on  the 
part  of  the  surrounding  tissues,  it  finally  exhausts  the  nutritive 
material  in  the  granulations  and  dies,  or  remains  in  a  latent  con- 
dition, the  granulation  material  is  converted  into  cicatricial  tissue, 
and  the  local  lesion  is  cured.  These  are  the  cases  which  terminate 
most  frequently  in  spontaneous  cure.  If  liquefaction  of  the  infected 
tissues  takes  place  and  the  products  of  degeneration  are  absorbed, 
a  similar  favorable  termination  is  possible.  If  the  same  product 


198      CLINICAL    FORMS    OF    SURGICAL     TUBERCULOSIS. 

is  evacuated  by  incision  nnder  antiseptic  precautions,  a  spontaneous 
cure  is  accelerated.  If,  on  the  other  hand,  a  secondary  infection 
with  pus- microbes  takes  place,  the  patient  incurs  the  danger  of 
septic  infection  and  local  and  general  dissemination  of  the  tuber- 
cular process. 

That  the  bacilli  do  not  grow  in  a  tubercular  abscess  has  been 
definitely  settled  by  Sehlegtendal  ("  Ueber  das  Vorkommen  der 
Tuberkel-bacillen  irn  Eiter,"  Fortschritte  der  Medizin,  Bd.  i.  S. 
537).  He  examined  five  hundred  and  twenty  specimens  of  pus 
from  tubercular  abscesses  and  found  bacilli  present  in  only  75  per 
cent.  Garre  (u  Aetiologie  der  kalten  Abscesse  ;  Driiseneiteruug  ; 
Weichtheil-  und  Knocheu-abscesse  uud  der  Tuberculosen  Gelen- 
keiterungen."  Deutsche  med.  Wochenschrift,  1886,  No.  34)  has 
also  made  an  extended  series  of  observations  to  ascertain  the  pres- 
ence of  the  tubercle  bacillus  in  cold1  abscesses.  According  to  this 
author,  many  tubercular  ulcerations  and  abscesses  are  the  result  of 
a  mixed  infection,  as  has  been  claimed  by  Hoffa  for  some  cases  of 
empysema  in  cases  of  pulmonary  or  pleural  tuberculosis.  In  cold 
abscesses,  and  in  the  pus  of  tubercular  cavities  in  bone,  no  pus- 
microbes  could  be  found,  not  even  in  cases  that  pursued  a  rapid 
course.  Cultivations  of  such  pus  remained  sterile,  while  inocula- 
tions produced  typical  tuberculosis.  In  such  instances  the  pus 
examined  under  the  microscope  showed  none  of  the  morphological 
elements  of  pus,  but  was  seen  to  consist  of  an  emulsion  composed 
of  detritus  of  broken-down  tissue  suspended  in  serum.  He  affirmed 
that  it  is  possible  that  in  many  cases  of  suppuration  following  in 
the  course  of  a  tubercular  process  pus  is  the  result  of  a  mixed 
infection,  and  that  the  pus-microbes  had  disappeared  before  the 
examination  was  made.  The  walls  of  the  tubercular  cavity  contain 
the  typical  structure  of  the  tubercular  lesion,  and  the  primary  and 
essential  cause  of  the  inflammation — the  bacillus  of  tuberculosis. 
The  infection  follows  the  migration  of  the  abscess  in  whatever 
direction  that  may  take  place.  If  an  additional  infection  from 
without  takes  place,  following  either  a  spontaneous  discharge  or 
after  incision,  the  superficial  granulations  are  destroyed  by  the  sup- 
purative  process  which  is  initiated,  exposing  the  patient  to  the 
additional  risks  of  septic  infection  and  a  more  rapid  local  and 
general  dissemination  of  the  tubercular  process. 


CHAPTEE    XVIII. 

ANTHRAX. 

SYNONYMS  :  Contagious  Carbuncle  ;  Charbon  ;  Milzbrand  ; 
Malignant  Pustule. 

HISTORY. — As  a  disease  among  animals  anthrax  has  been 
known  since  the  earliest  records  of  history.  The  contagiousness 
of  this  disease  has  been  recognized  since  the  beginning  of  the 
eighteenth  century.  During  the  first  part  of  this  century  it  was 
described  as  a  blood  disease  (Maladie  du  sang.  Blutseuche  der 
Schafe).  Heusiuger,  in  his  classical  work  (Die  Milzbrandkrank- 
heiten  der  Thiere  und  des  Menschen,  Erlaugen,  1850),  declared 
anthrax  to  be  a  malarial  neurosis.  In  the  year  1855  Polleuder 
("  Mikroskop.  und  Mikrocheni.  Untersuchungen  des  Milzbrand - 
blutes,  etc.,'7  Casper' s  Vierteljahrsschriftf.  ger.  u.  off.  Medizin,  Bd. 
viii.  S.  103)  published  his  discoveries,  which  inaugurated  a  new  era 
in  the  study  of  anthrax.  As  early  as  1849  he  had  discovered  in 
the  blood  of  cattle  suffering  from  anthrax  a  mass  of  innumerable 
fine  rod-like  bodies,  which  appeared  to  be  of  a  vegetable  nature 
and  resembled  vibriones.  Brauell  ("Versuche  und  Untersuch- 
ungen betreifend  den  Milzbrand  des  Menscheu  und  der  Thiere," 
Vlrchow's  Archiv,  No.  xi.,  1857)  found  the  same  organisms  in  the 
blood  of  men,  horses,  and  sheep  which  had  died  of  anthrax. 
He  also  found  the  same  bodies  during  life  in  the  blood  of  the 
diseased  animals. 

Delafond  (Recueil  de  med.  vet.,  1860,  p.  726)  considered  this 
parasite  as  a  kind  of  leptothrix. 

In  1863  appeared  the  work  of  Davaine  (Compt.  rend,  de  VAcad. 
des  Sciences,  t.  Iviii.  p.  22)  wherein  he  pronounced  these  rod-like 
bodies  to  be  bacteria,  and  later  he  called  them  bacteridia.  He 
believed  them  to  be  the  cause  of  anthrax,  as  the  disease  could  not 
be  propagated  with  blood  which  did  not  contain  them. 

Through  the  labors  of  Naegeli  and  Bollinger  (Zur  Pathologie 
des  Mikbrandes.  Miincheu,  1872)  and  others  the  microorganism 
of  anthrax  finally  found  a  permanent  place  as  the  bacillus  anthracis 
among  the  schizomycetes. 

The  first  positive  accounts  of  the  disease  in  man  we  owe  to 
Foamier,  Montfils,  Thomassin,  and  Chabert,  who  published  their 
description  between  the  years  1769  and  1780.  Fournier  first  dis- 


200  ANTHRAX. 

tinguished  the  spontaneous  and  the  communicated  carbuncle  of 
man.  The  primary  existence  of  anthrax  in  man  was  asserted  by 
Bayle  in  1800  and  by  Davy  la  Chevrie  in  1807. 

DESCRIPTION  OF  THE  BACILLUS  OF  ANTHRAX. — Rods  5-10 
micromillimetres  long,  and  1—1.25  micromillimetres  broad,  and 
threads  made  up  of  rods  and  cocci.  The  rods,  as  a  rule,  are  straight, 
only  when  they  grow  to  a  considerable  length  and  meeting  \vith  re- 
sistance they  become  curved.  The  rods  and  threads  are  round,  and 
with  their  ends  truncated  at  right  angles  appear  as  though  they 
had  been  cut  off  obliquely.  The  interior,  as  long  as  fission  does 
not  proceed,  is  perfectly  homogeneous  and  absorbs  aniline  dyes 
very  readily.  The  development  of  spores  in  long  undivided 
threads,  as  we  find  them  in  fluid  culture  media,  takes  place  at 
regular  intervals,  where  we  find  them  as  bright  oval  spots  which 
become  more  and  more  apparent,  marking  the  direction  of  the  rods. 
Upon  solid  culture  media  the  development  of  spores  is  preceded 
by  transverse  segmentation  of  the  rods.  The  cell-membrane  of 
each  section  finally  becomes  the  membrane  of  the  spore,  each  pole 
of  the  spore  presenting  a  small  mass  of  protoplasm  which  can  be 
stained. 

STAINING. — Cover-glass  preparations  of  fluid  specimens  can  be 
stained  with  a  watery  solution  of  any  of  the  aniline  dyes.  They 
can  be  rapidly  stained  with  a  drop  of  fuchsin  or  gentian-violet,  but 
more  satisfactorily  by  floating  the  cover-glass  for  twenty-four  hours. 
The  preparations  are  dried  and  mounted  in  Canada  balsam.  The 
spores  are  not  stained  by  the  ordinary  methods.  Tissue  sections 
are  best  stained  by  Gram's  method,  and  after-stained  with  eosiu, 
picrocarminate  of  ammonium.  By  double  staining  the  rods  are 
seen  to  consist  of  a  hyaline  sheath  with  protoplasmic  contents. 

CULTIVATION. — a.  G-elatin.  If  a  nutrient  medium  of  5  to  8 
per  cent,  of  gelatin  is  inoculated,  a  whitish  line  develops  in  the 
track  of  the  needle  puncture,  and  from  it  fine  filaments  spread  out 
on  the  sides.  In  a  more  solid  nutrient  gelatin,  the  growth  appears 
only  as  a  thick,  white  thread.  The  culture  liquefies  the  gelatin, 
and  the  growth  subsides  as  a  white  flocculent  mass. 

b.  Agar-agar.     Cultures    upon   a   sloping   surface  of  nutrient 
agar-agar  form  a  viscous  snow-white  plaque.     Without  access  of 
air  the  culture  does  not  grow,  the  bacilli  being  aerobic. 

c.  Potato.     Inoculation  of  sterilized  potato  yields  a  very  char- 
acteristic growth.     The  deep  chamber,  containing  the  potato,  is 
placed  in  the  incubator,  and  in  about  thirty-six  or  forty-eight  hours 
a  creamy,  very  faintly  yellowish  layer  forms  over  the  inoculated 
surface,  with  usually  a  peculiar  translucent  edge.     On  removing 
the  cover  of  the  damp  chamber  a  strong,  penetrating  odor  of  sour 
milk  is  emitted. 


PLATE    IX. 


!  i 


a. 


b. 


Two  cultures  of  anthrax  bacilli  prepared  from  the  same  material 
at  the  same  time. 

a.  With  a  pressure  of  4  cm.  of  mercury. 

b.  With  atmospheric  pressure. 


ATTENUATION    OF    VIRUS.  201 

INOCULATION  EXPERIMENTS. — In  order  to  cause  death  of  ani- 
mals by  inoculation  of  the  bacillus  of  anthrax,  the  pure  culture,  or 
anthracic  blood,  must  be  injected  into  the  subcutaneous  tissue,  into 
the  circulation,  or  the  virus  may  be  transmitted  by  inhalation  or 
by  feeding.  Goats,  hedgehogs,  sparrows,  cows,  horses,  guinea-pigs, 
and  sheep,  can  be  readily  infected.  Eats  are  less  susceptible.  Pigs, 
dogs,  cats,  white  rats,  and  Algerian  sheep  are  immune.  Frogs  and 
fish  have  been  rendered  susceptible  by  raising  the  temperature  of 
the  water  in  which  they  lived. 

ATTENUATION  OF  VIRUS. — By  cultivating  the  bacillus  in  neu- 
tralized bouillon  at  42°-43°  C.  (107.6°-109.4°  F.)  for  about 
twenty  days  the  infecting  power  is  weakened  and  animals  inocu- 
lated with  it  are  protected  against  the  disease.  A  still  greater 
immunity  is  obtained  by  inoculating  a  second  time  with  material 
which  has  been  less  weakened.  The  animals  are  then  protected 
against  the  most  virulent  form  of  anthrax,  but  only  for  a  time.  A 
temperature  of  55°  C.  (131°  F.),  or  treatment  with  5  to  1  per  cent, 
solution  of  carbolic  acid  deprives  the  bacilli  of  their  virulence. 
The  virulence  of  the  bacillus  is  also  altered  by  passing  it  through 
different  species  of  animals. 

Woolbridge  secured  immunity  against  anthrax  in  animals  by 
cultivating  the  bacillus  in  an  alkaline  solution  at  a  temperature  of 
37°  C.  (98.6°  F.)  for  two  days.  At  this  time  the  fluid  was  filtered 
and  a  small  quantity  of  the  filtrate  injected  into  the  subcutaneous 
tissue  of  rabbits,  which  remained  well,  and  subsequently  resisted 
injection  of  most  virulent  authracic  blood. 

Hankin  ("  Immunity  produced  by  an  Albuminose  isolated  from 
Anthrax  Cultures/'  British  Med.  Journal,  Oct.  12,  1889),  under  the 
guidance  of  Koch  at  the  Hygienic  Institute  of  Berlin,  isolated  an 
albumose  from  anthrax  cultures  which,  when  injected  into  rabbits 
and  mice  in  small  quantities,  rendered  these  animals  immune  against 
the  most  virulent  cultures.  The  albumose  was  prepared  from  the 
cultures  by  precipitation  with  absolute  alcohol,  the  precipitate  was 
well  washed  in  this  liquid  to  free  it  from  ptomaines,  since  it  is 
known  that  all  such  substances  are  soluble  in  alcohol.  After  the 
addition  of  alcohol  it  was  filtered  off  and  dried,  then  redissolved, 
and  filtered  through  a  Chamberland's  filter.  Four  rabbits  were 
inoculated  with  virulent  anthrax  spores  and  three  of  them  received 
an  injection  of  albuminose  into  the  ear-vein  at  the  same  time;  the 
latter  recovered,  while  the  remaining  animal  not  thus  protected 
died  in  about  forty-eight  hours  of  anthrax.  In  another  experi- 
ment, ten  mice  were  each  injected  with  the  millionth  part  of  their 
body-weight  of  anthrax  albuminose  and  with  active  vaccine  at  the 
same  time.  Of  these,  three  died  after  108  to  116  hours;  the  others 
recovered.  Three  others  had  only  the  two-milliouths  of  their  body- 


202  ANTHRAX. 

weights  of  anthrax  albuminose  and  active  culture.  Two  of  them 
survived.  Four  control  mice  were  inoculated,  and  all  died  of 
anthrax.  He  has  come  to  the  conclusion  that  when  a  large  dose 
of  albuminose  is  injected  into  an  animal,  the  entry  of  anthrax 
bacilli  into  the  system  is  aided,  and  when  a  small  dose  is  adminis- 
tered immunity  is  acquired  against  its  poisonous  properties,  protect- 
ing the  animal  against  subsequent  inoculations  with  active  cultures. 

INTENSIFICATION  OF  VIRUS. — While  it  is  known  that  some 
chemical  substances  exert  an  attenuating  influence  on  the  virulence 
of  the  anthrax  bacillus,  it  has  also  been  found  that  an  attenuated  virus 
will  again  become  more  virulent  by  adding  certain  substances.  It 
must,  therefore,  be  taken  for  granted  that  the  chemical  composition 
in  which  the  bacillus  is  suspended  influences  in  one  way  or  the  other 
its  virulence.  It  has  been  found,  for  instance,  that  the  addition 
of  a  minute  quantity  of  lactic  acid  to  a  fluid  containing  the  bacillus 
in  an  attenuated  form  greatly  intensifies  its  virulence  within  a  very 
short  time.  Thus,  Arloiug,  Corneviu,  and  Thomas  found  that  the 
pathogenic  power  of  a  fluid  containing  these  bacilli,  to  which  -g-J-Q- 
part  of  lactic  acid  had  been  added,  and  the  mixture  allowed  to 
stand  for  twenty-four  hours/was  increased  twofold  ;  if  then  a  little 
water,  containing  a  very  easily  fermentable  sugar  is  added  to  the 
mixture,  and  another  twenty-four  hours  allowed  to  elapse,  the  viru- 
lence attains  its  maximum,  and  frogs  inoculated  with  this  virus  die 
in  from  twelve  to  fifteen  hours,  whereas,  when  inoculated  with 
ordinary  virus  they  live  from  forty  to  fifty  hours.  Kitt  has 
repeated  and  confirmed  these  experiments. 

ANTHRAX  INFECTION  IN  MAN,  AND  CLINICAL  VARIETIES. — 
The  favorite  location  for  the  development  and  growth  of  the  bacillus 
of  anthrax  in  man  and  beast  is  in  the  connective  tissue  ;  it  is,  there- 
fore, immaterial  in  what  manner  the  microorganism  reaches  this 
tissue,  as  localization  here  marks  the  beginning  of  the  disease. 
Buchner  ("  Ueber  Aufnahme  von.  Infectionserregern  durch  die 
iutacte  Luugeuoberfliiche,"  Verh.  des  Congress  f.  innere  Mediciri, 
1888)  has  studied  experimentally  the  entrance  of  the  bacillus  of 
anthrax  through  the  intact  surface  of  the  lung.  The  bacillus  and 
spores  were  administered  by  inhalation  in  the  shape  of  dry  powder 
and  suspended  in  steam.  On  examining  the  bronchial  mucous 
membrane  at  different  stages  under  the  microscope  it  was  seen  that 
the  spores  were  transformed  in  a  very  short  time  into  bacilli,  and 
that  the  latter,  by  their  growth,  pushed  themselves  between  the 
cells  and  into  the  capillary  vessels.  It  was  observed  that  the 
greater  the  pulmonary  irritation  was,  the  more  the  passage  of  the 
microbes  was  retarded.  The  entrance  of  the  bacilli  from  the  sur- 
face of  the  mucous  membrane  into  the  capillary  vessels  was  seen  to 
depend  on  an  active  process.  Only  blood  bacilli,  to  which  belong 


PLATE    X. 


Development  of  anthrax  spores.  Culture  three  days  old  ;  cultivated 
at  40°  C.  (104°  F.)  on  meat-peptone-agar.  Gentian-iodine.  Zeiss  T\. 
O.  4.  Magnified  2500  diam. 

a.  Threads  free  from  spores. 

b.  Threads  with  beginning  development  of  spores. 

c.  Threads  with  perfect  development  of  spores. 


INFECTION    IN    MAN    AND    CLINICAL    VAKIETIES.       203 

the  bacillus  of  anthrax  and  the  spirilli  of  recurrent  fever,  possess 
this  property.  The  tubercle  bacillus  and  the  bacillus  of  glanders 
are  no  blood  bacilli,  but  even  in  infective  processes  with  these 
microbes  the  disease  can  be  produced  by  inhalation  without  primary 
localization  in  the  lungs.  Entrance  of  these  microbes  into  the  blood 
without  alteration  of  the  vessel  wall  has  not  been  proved.  Anthrax 
on  the  external  surface  of  the  body  is  the  result  of  direct  inocula- 
tion. The  clinical  forms  vary  according  to  the  location  of  the  dis- 
ease, its  extent,  and  the  intensity  of  the  infection.  Most  all  authors 
follow  Bollinger's  classification,  according  to  which  all  cases  are 
brought  under  one  of  the  following  varieties:  1.  Anthrax  acutissi- 
mus,  or  apoplectiformis.  2.  Acutus ;  and  3.  Subacutus.  The 
primary  location  of  the  disease  is  in  accordance  with  the  manner  in 
which  infection  has  taken  place.  W.  Koch  ("  Milzbrand  u.  Rausch- 
brand,"  Deutsche  Chirurgie,  Lieferung  9)  states  that  in  animals  and 
man  the  bacillus  can  enter  the  organism  through  one  of  the  follow- 
ing three  routes  :  (a)  Through  the  skin.  (6)  Gastro -intestinal 
canal,  (c)  Respiratory  passages.  The  microbe  first  multiplies  at 
the  primary  point  of  invasion,  and  from  here  by  entering  the  blood- 
vessels it  is  conveyed  to  distant  parts  and  organs.  The  pathologico- 
anatomical  conditions  vary  according  to  the  primary  seat  of  invasion 
and  the  structure  of  the  organ  the  seat  of  the  disease.  The  first 
tissue-changes  are  observed  at  the  primary  seat  of  localization. 
These  local  conditions,  carbuncle  and  anthrax-oedema,  give  rise  to 
symptoms  proportionate  to  the  importance  of  the  organ  involved. 
An  anthrax  oedema  of  the  hand  or  arm  is  a  less  serious  condition 
than  when  the  same  affection  involves  the  face  or  neck.  The  local 
oedema  at  the  point  of  infection  is  caused  by  vascular  disturbances 
due  to  the  presence  of  the  bacilli  within  the  bloodvessels  and  the 
interstitial  inflammatory  exudation  caused  by  their  presence.  The 
local  affection  always  becomes  dangerous  when  the  bacillus  enters 
the  bloodvessels  and  gives  rise  to  general  dissemination.  When 
the  microorganism  enters  the  body  through  the  gastro-intestinal 
canal  with  the  food  or  drink,  it  gives  rise  to  a  primary  anthrax  of 
the  intestinal  canal,  which  again  may  become  general  by  metastatic 
dissemination  through  the  systemic  circulation. 

Vierhoff  (  Ueber  Anthrax  intestinalis  beim  Menschen,  Dissertation, 
Dorpat,  1885)  has  collected  41  cases  of  anthrax  intestinalis,  the 
total  number  which  were  found  reported  up  to  1885.  The  author 
observed  himself  two  cases  of  secondary  intestinal  anthrax  in  the 
hospital  at  Liga. 

Cases  of  secondary  intestinal  anthrax — that  is,  localization  of  the 
bacillus  of  anthrax  in  the  mucous  membrane  of  the  intestines  after 
external  infection — were  known  to  the  older  authors,  while  obser- 


204  ANTHKAX. 

vatioDS  of  primary  localization  in  the  digestive  tract  date  only  from 
the  middle  of  the  last  century. 

Of  63  cases  of  anthrax  in  man,  collected  by  Slessarewskji  (Amer. 
Journ.  Med.  Sciences,  1887),  the  disease  showed  itself  6  times  on 
the  face,  21  on  the  neck,  and  36  in  other  places.  Various  theories 
have  been  advanced  in  explanation  of  the  immediate  cause  of  death 
of  animals  and  persons  infected  with  anthrax.  In  the  most  viru- 
lent form,  the  anthrax  acutissimus,  Bollinger  believes  that  the  rapid 
growth  of  the  bacillus  in  the  blood  brings  about  a  sudden  diminu- 
tion of  oxygen  and  a  surplus  of  carbonic  acid,  and  that  death  takes 
place  by  a  slow  process  of  asphyxia.  Against  this  theory  it  can  be 
maintained  that  in  the  blood  of  animals  which  have  died  of  the 
acutest  form  of  the  disease  very  few  bacilli  can  be  found;  and 
further,  that  in  the  experiments  made  by  Nencki  on  the  blood  of 
rabbits  which  had  died  of  this  form  of  anthrax  it  was  found  as 
capable  of  oxygenation  as  the  blood  of  healthy  animals.  The 
theory  that  death  results  from  purely  mechanical  causes  due  to  the 
presence  of  bacilli  in  great  abundance  in  the  bloodvessels  is  like- 
wise not  tenable,  because  no  such  fatal  degree  of  obstruction  in  the 
capillary  circulation  has  been  found  at  the  post-mortem  examina- 
tions. 

As  a  third  hypothesis,  Bollinger  advanced  that  the  bacillus  may 
generate  a  chemical  poison  which  may  cause  death  by  intoxication. 

In  reference  to  the  last-mentioned  cause,  Hoifa  (Die  Natur  des 
Milzbrandgiftes,  Wiesbaden,  1886)  calls  attention  to  the  following 
three  possibilities: 

1.  The  bacilli  of  anthrax  are  in  themselves  poisonous,  and  with 
the  increase  in  their  number  the  quantity  of  the  poison  is  increased 
in  the  same  ratio.     Against  this  supposition  the  results  of  the  ex- 
periments made  by  Hoffa,  himself,  furnish  the  most  conclusive 
proof.     Of  a  pure  culture  of  anthrax  bacilli  he  injected  a  large 
quantity  directly  into  the  jugular  vein  of  rabbits.     The  animals 
thus  infected  showed  no  symptoms  of  acute  intoxication,  but  died 
in  the  same  manner  as  animals  infected  in  the  usual  manner. 

2.  The  bacilli  of  anthrax  produce  a  poison  capable  of  producing 
fermentation  in  the  blood,  and  which  is  soluble  in  the  blood.     The 
fact  that  filtered  blood  of  animals  which  had  died  of  anthrax  did 
not  produce  toxic  symptoms  when  injected  into  healthy  animals 
speaks  against  this  argument. 

3.  The  bacillus  of  anthrax  separates  toxic  substances  from  com- 
plex combinations  in  the  organism.    This  last  explanation  appears, 
from  analogy  of  the  views  that  are  now  entertained  of  bacteria  and 
ptomaines,  to  be  the  most  plausible,  and  Hoffa  went  at  the  task  to 
produce  such  substances  outside  of  the  animal  body  upon  artificial 
culture  media.     For  this  purpose  he  cultivated  the  bacillus  with 


ANTI-MICKOBIC    TREATMENT    OF    ANTHRAX.        205 

the  greatest  precautions  upon  sterilized  meat  kept  for  several  weeks 
in  an  incubator  at  87°  C.  (98.6°  F.).  The  chemical  product  he 
attenuated  according  to  the  methods  advised  by  Stass-Otto,  Brieger, 
and  after  the  more  recent  methods  of  Fischer.  By  the  methods  of 
Stass-Otto  and  Fischer  he  succeeded  in  finding  a  substance  which 
possessed  an  alkaline  reaction,  and  which  produced  toxic  effects  in 
animals.  A  strictly  pure  article  and  an  accurate  chemical  descrip- 
tion of  it  could  not  be  obtained  on  account  of  the  smalluess  of  the 
quantity  which  could  be  produced.  By  Brieger's  method,  cultiva- 
tions upon  sterilized  yolk  of  egg  diluted  with  sterilized  water,  it 
was  found  impossible  to  obtain  a  toxic  substance. 

The  substance  produced  by  Stass-Otto's  method  was  used  in 
experimenting  on  frogs,  mice,  guinea-pigs,  and  rabbits,  and  that 
obtained  by  Brieger's  method  on  guinea-pigs  and  rabbits,  and  both 
of  them  produced  symptoms  of  intoxication.  After  a  short  period 
of  intoxication  with  increased  action  of  the  heart  and  accelerated 
respiration  the  animals  became  somnolent,  respirations  deep,  slow, 
and  irregular,  assisted  by  the  action  of  all  accessory  muscles  of 
respiration;  pupils  dilated ;  temperature  below  normal;  diarrhoea; 
feces  bloody ;  speedy  death.  At  the  necropsy  the  heart  was  found 
contracted,  the  blood  was  of  a  dark  color,  and  ecchymoses  of  the 
pericardium  and  peritoneum  existed;  there  were  no  microorgan- 
isms in  the  blood;  no  such  toxic  substance  could  be  produced  from 
sterilized  meat  alone.  The  same  author  ("  Zur  Lehre  der  Sepsis," 
Verh.  d.  deutsohen  G-esellschaft  f.  Chirurgie,  1889)  subsequently 
succeeded  in  isolating  a  toxic  substance  from  the  bodies  of  anthracic 
rabbits  with  the  formula  of  C3H6N2,  which  he  called  anthraciu, 
and  to  which  he  attributed  the  toxic  symptoms  in  cases  of  anthrax. 
Injected  subcutaneously  in  rabbits  it  produced  first  restlessness, 
rapid  pulse  and  respiration,  followed  by  somnolence,  deeper  and 
slower  respiration,  diarrhoea,  asphyctic  symptoms,  convulsions,  and 
death.  These  experiments  leave  but  little  doubt  that  the  fatal 
termination  in  cases  of  anthrax  is  due  to  the  presence  of  ptomaines, 
which  are  formed  in  the  body  in  consequence  of  the  action  of  the 
bacilli  upon  certain  complex  combinations  in  the  organism. 

Anti-microbic  Treatment  of  Anthrax. 

Lande  (Memoires  de  la  Societe  de  Mtdecine  de  Bordeaux,  1889) 
reports  two  cases  of  malignant  anthrax  saved  by  subcutaneous  injec- 
tions of  carbolic  acid.  In  the  first  case,  a  man  aged  twenty-seven 
years,  the  upper  lip  was  the  seat  of  the  carbuncle ;  in  the  second,  a 
woman  aged  sixty-five  years,  the  anthrax  occupied  the  region  below 
the  scapula.  Both  patients  were  very  ill,  low  delirium  and  other 
symptoms  of  toxaemia  being  present.  The  injections  were  made 


206  ANTHKAX. 

into  the  subcutaneous  tissue  around  the  carbuncle.  The  strongest 
solution  used  consisted  of  15  grammes  of  neutral  glycerin  and  an 
equal  part  of  distilled  water,  in  which  3  grammes  of  pure  carbolic 
acid  were  dissolved.  The  injections  were  made  at  five  points  around 
the  anthrax,  and  represented  a  total  dose  of  50  centigrammes  of  the 
acid.  The  injections  were  painful,  but  rapid  improvement  followed. 
This  10  per  cent,  solution  was  stronger  than  any  previously  em- 
ployed for  the  same  purpose  by  Boeckel,  Kaimbert,  and  others.  A 
5  per  cent,  solution  in  ordinary  cases  is  strong  enough,  but  in  grave 
cases  the  10  per  cent,  solution  must  be  used  until  improvement 
takes  place,  which  may  occur  within  forty-eight  hours. 

Kaloif,  of  St.  Petersburg,  in  making  experiments  with  anthrax 
on  animals,  accidentally  infected  himself,  either  by  a  needle  punc- 
ture or  by  handling  the  organs  of  anthracic  animals.  The  local 
infection  appeared  on  the  outer  side  of  the  thumb  of  the  left  hand 
as  a  small  vesicle,  which  disappeared  soon,  but  gave  place  to  circum- 
scribed infiltration  on  the  second  day.  This  inflammation  rapidly 
extended  and  was  surrounded  with  hemorrhagic  vesicles.  The  in- 
durated tissues  were  promptly  removed  by  excision ;  nevertheless, 
on  the  next  day  swelling  of  axillary  glands  on  the  same  side,  fever, 
great  prostration,  also  diarrhoea.  The  skin  in  the  axillary  region 
and  the  side  of  chest  was  much  swollen,  cedematous,  and  at  different 
points  bright  red,  at  others  bluish-red.  One  of  the  axillary  glands 
the  size  of  a  hen's  egg,  and  glands  along  the  margins  of  the  pector- 
alis  major  were  moderately  enlarged.  All  the  enlarged  glands  were 
removed  and  the  field  of  operation  thoroughly  disinfected  with 
solution  of  carbolic  acid,  and  the  same  solution  thrown  into  the 
surrounding  tissues  with  a  hypodermic  syringe.  Cessation  of  fever 
and  rapid  healing  of  wound,  followed  by  recovery.  Implantations 
of  fragments  of  excised  glands  in  bouillon  and  gelatin  yielded 
cultures  of  anthrax  bacilli.  Excision  of  infected  tissue  and  use  of 
carbolic  acid  strongly  recommended. 


PLATE    XI. 


m 

\ 


Spleen  of  rabbit-anthrax. 

a.  Pulp. 

b.  Follicle. 

c.  Vein. 


CHAPTEE    XIX. 

GLANDERS  (Malleus  Humidus}. 

ALTHOUGH  glanders  in  man  is  a  rare  affection,  it  presents  from 
a  bacteriological  study  so  many  points  of  interest  that  it  merits 
more  than  a  passing  notice.  It  is  one  of  the  infection^  diseases  of 
which  the  microbic  cause  is  now  thoroughly  understood. 

HISTORY. — That  glanders  in  man  occurs  as  an  infection  from 
animals  has  been  known  for  a  long  time.  Its  contagiousness  among 
horses  was  asserted  by  Solleysel  in  the  seventeenth  century.  Rind- 
fleisch  believed  that  he  saw  vibriones  in  the  granular  contents  of 
glanderous  abscesses.  Klebs  detected  in  cultures  of  pus  taken  from 
animals  suffering  from  this  disease  small  rods  and  granules,  but 
further  cultivations  and  inoculations  in  rabbits  failed.  The  pres- 
ence of  minute  organisms  in  cases  of  glanders  was  pointed  out  by 
MM.  Christatt  and  Kiener,  in  1868,  and  their  observations  were 
corroborated  by  MM.  Bouchard,  Capitan,  and  Charrin,  who  have 
found  the  organisms  not  only  in  parts  exposed  to  the  air,  such  as 
nasal  ulcerations  and  pulmonary  abscesses,  but  also  in  parts  which 
are  not  so  exposed,  such  as  the  spleen,  liver,  and  lymphatic  glands. 

Chaveau  (Comptes  rendus,  Ixvii.,  ISTo.  14)  demonstrated  by  his 
experiments  that  the  virus  of  glanders  was  fixed  to  small  solid 
particles,  as  he  found  the  sediment  which  formed  after  diluting  pus 
with  water  active.  This  discovery  marked  an  advance  in  the 
knowledge  of  the  physical  nature  of  the  virus.  Loffler  and  Schiitz 
are  the  discoverers  of  the  bacillus  of  glanders  in  horses.  In  1882 
they  made  a  preliminary  report  of  their  researches  (Deutsche  med. 
Wochenschrift,  1882,  No.  52).  In  1886  Loffler  published  his  elab- 
orate monograph  on  this  subject  ("  Die  Aetiologie  der  Rotzkrank- 
heit,"  Arbeiten  cms  dem  Kaiserlicken  Gresundheitsamte  zu  Berlin, 
B.  i.  S.  141-199).  Soon  after  Loffler's  first  paper  appeared, 
Bouchard,  Capitan,  and  Charrin  published  almost  simultaneously 
the  results  of  their  researches  and  observations  ;  but  it  appears  from 
Loffler's  second  paper  that  none  of  them  had  been  able  to  produce 
a  pure  culture.  Kitt  and  Weichselbaum  were  the  first  who,  by 
their  own  labor,  were  able  to  corroborate  the  correctness  of  Loffler's 
discovery ;  the  former  by  his  observations  and  experiments  on 
animals,  the  latter  by  a  case  of  glanders  in  the  human  subject  that 
came  under  his  observation. 


208 


GLANDERS. 


DESCRIPTION  OF  THE  BACILLUS  MALLEI. — According  to  Loffler, 
the  bacillus  of  glanders  appears  as  a  small  rod  which  is  somewhat 
shorter  and  thicker  than  the  tubercle  bacillus ;  its  length  varies  but 
little,  and  corresponds  to  about  two-thirds  of  the  diameter  of  a  red 
blood-corpuscle ;  the  thickness  varies  between  one-fifth  and  one- 
eighth  of  its  length  (Fig.  7.)  These  bacilli  are  either  straight  or 
somewhat  curved  and  rounded  at  their  ends.  Usually  they  are 
found  in  pairs  in  a  parallel  direction  held  together  by  a  delicate 
unstained  substance.  Examined  in  a  drop  of  fluid  they  showed 
active  molecular  movements.  Spontaneous  movements  could  not 
be  observed  by  Loffler.  The  colorless  and  sometimes  even  some- 
what dilated  portions  of  the  stained  bacillus  are  not  spores,  but,  as 

FIG.  7. 


Bacilli  of  glanders,    a.  Section  from  glandrous  nodule,  700  :  1.     b.  Bacilli  of  glanders, 
stained  with  methyl-blue.     (FLUGGE.) 

Loffler  affirms,  are  indications  of  commencing  death  of  the  microbe. 
Loffler  found  that  dry  bacilli  occasionally  could  be  made  to  grow 
after  three  months,  but  in  most  instances,  after  a  few  weeks,  they 
could  no  longer  be  cultivated,  which  fact  speaks  against  the  exist- 
ence of  spores.  Lundgren  saw  the  bacilli  in  an  agar-agar  culture 
multiply  by  segmentation. 

STAINING. — The  manner  of  staining  of  the  bacilli  of  glanders  is 
characteristic,  as  when  they  are  treated  by  basic  and  acid  aniline 
dyes  no  effect  is  produced. 

Method  of  Schutz :  The  sections  are  placed  for  twenty-four  hours 
in  the  following  mixture :  Potash  solution  (  1  in  10,000),  concen- 
trated alcohol,  methylene-blue  solution,  equal  parts.  Wash  the 
sections  in  a  watch-glass  with  water  acidulated  with  four  drops  of 


INOCULATION    EXPERIMENTS.  209 

acetic  acid.     Transfer  for  five  minutes  to  fifty  per  cent,  alcohol, 
clarify  in  clove-oil,  and  mount  in  Canada  balsam. 

Loffler*8  method:  Sections  are  immersed  for  a  few  minutes  in  a 
solution  of  potash  1  to  10,000,  then  for  a  few  minutes  in  an  alka- 
line solution  of  methyl-blue,  after  which  they  are  decolorized  with 
a  solution  of  tropseolin  in  acetic  acid,  or,  what  is  still  better,  in  a 
fluid  composed  often  cubic  centimetres  of  distilled  water,  two  drops 
of  sulphuric  acid,  and  one  drop  of  a  five  per  cent,  solution  of  oxalic 
acid. 

CULTIVATION. — When  cultivated  on  solid  sterilized  blood  serum 
at  a  temperature  of  38°  C.  (100.4°  F.),  the  growth  appears  in  the 
form  of  minute  transparent  drops,  consisting  entirely  of  the  charac- 
teristic bacilli. 

Potato  cultures,  according  to  Loffler,  form  in  three  days  a  uniform 
amber-yellow  layer  which,  about  the  sixth  to  the  eighth  day,  assumes 
a  reddish  hue,  resembling  the  color  of  oxide  of  copper,  which  is  not 
easily  mistaken  for  any  other  culture  upon  the  same  soil.  Upon 
this  soil  the  bacilli  were  cultivated  through  twelve  generations,  and 
the  cultures  retained  their  activity  for  a  year;  whether  the  bacillus 
was  capable  of  cultivation  after  this  time  is  not  mentioned.  The 
temperature  at  which  cultures  could  be  made  to  grow  varied  from 
30°  to  40°  C.  (86°  to.  104°  F.). 

Kranzfeld  succeeded  best  with  a  nutrient  medium  composed  of 
meat-peptone,  glycerin,  agar-agar.  The  bacillus  is  destroyed  by 
exposure  for  ten  minutes  to  a  temperature  of  55°  C.  (131°  F.).  A 
three  per  cent,  solution  of  carbolic  acid,  a  one  per  cent,  solution  of 
permanganate  of  potash,  or  a  1  :  5000  solution  of  corrosive  subli- 
mate destroys  the  bacilli  with  certainty.  Lundgren  succeeded  in 
obtaining  an  active  culture  in  bouillon. 

INOCULATION  EXPERIMENTS. — Kitt  ("Der  Eauschbrand,  Zu- 
sammenfassende  Skizze  iiber  den  gegenwartigen  Stand  der  Literatur 
n lid  Pathologic,"  Centralblatt  fur  Bacteriologie  und  Parasitenkunde, 
Bd.  i.  S.  722,  1887)  mentions  the  following  animals  susceptible  of 
inoculation  with  the  virus  of  glanders  :  catttle,  sheep,  goats,  guinea- 
pigs.  The  horse,  ass,  and  white  rat  are  only  susceptible  to  local 
infection,  the  animals  recovering  completely  and  permanently  after 
a  few  days.  Pigs,  dogs,  cats,  rabbits,  the  common  rat,  ducks,  and 
chickens  possess  great  immunity ;  the  inoculations  at  best  produce 
only  a  slight  local  reaction.  Loffler  made  his  first  experiments  on 
guinea-pigs  and  the  field  mouse.  In  the  guinea-pigs  he  observed, 
three  to  five  days  after  the  subcutaneous  injection  of  a  pure  culture, 
an  ulcer  at  the  point  of  inoculation,  and  at  the  end  of  the  first  week 
swelling  of  the  nearest  lymphatic  glands  in  a  state  of  purulent  soft- 
ening. At  this  stage  of  the  disease  the  process  often  came  to  a 
standstill  and  the  animals  recovered.  In  many  animals  the  disease 

14 


210  GLANDERS. 

progressed  quite  rapidly  to  a  fatal  termination.  Abscesses  were 
frequently  found  in  the  testicle  and  the  epididymis  in  the  male,  and 
in  the  breast  and  external  genital  organs  of  the  female.  The  face, 
nasal  cavity,  and  ankle-joint  were  also  frequently  the  seat  of  nlcer- 
ative  processes.  If  the  disease  proved  fatal,  death  usually  occurred 
three  or  four  weeks  after  the  inoculation.  At  the  post-mortem, 
aside  from  the  affections  which  have  been  enumerated,  nodules  were 
found  in  the  spleen,  lungs,  and  often  also  in  the  liver.  Field  mice 
proved  a  great  deal  more  susceptible  to  the  virus  of  glanders,  than 
guinea-pigs,  as  they  usually  died  three  or  four  days  after  inocula- 
tion. The  post-mortem  in  these  animals  showed  at  the  point  of 
inoculation  an  infiltration  from  which  swollen  lymphatic  vessels 
led  to  the  nearest  lymphatic  glands.  In  the  spleen  and  liver, 
which  were  always  greatly  enlarged,  numerous  small  nodules  were 
found,  while  the  remaining  internal  organs  presented  a  normal 
appearance.  Glanders  in  guinea-pigs  and  field  mice  presents  a 
series  of  pathological  changes  which  cannot  be  mistaken  for  any 
other  affection.  The  bacilli  of  glanders  in  the  different  organs  can 
be  detected  most  readily  in  recent  specimens.  In  the  blood  bacilli 
were  found  only  in  very  acute  cases,  a  circumstance  which  explains 
why  so  many  inoculations  with  the  blood  of  glanderous  horses 
proved  unsuccessful. 

Lundgreu  ("  Forsok  till  remodliug  af  rots-mikrobeu,"  Hygiea, 
Bd.  xlix.,  Heft  2,  S.  91)  took  a  nodule  from  the  lungs  of  a  horse 
which  had  died  of  glanders  and  implanted  fragments  of  it  under 
the  skin  of  rabbits.  The  animals  died  about  the  nineteenth  day 
after  the  inoculation,  and  the  necropsy  revealed  induration  and 
small  abscesses  at  the  point  of  infection,  and  small  yellow  nodules 
in  the  spleen,  liver,  lungs,  testicles,  and  mucous  membrane  of  the 
nose.  These  tissues  stained  with  methyl-blue  showed  the  bacilli  of 
glanders.  Implantations  of  spleen  tissue  into  other  rabbits  fixed 
the  period  of  incubation  in  this  animal  at  from  eleven  to  twelve  days. 

At  a  recent  meeting  of  the  Academy  of  Medicine,  M.  Cornil 
(British  Medical  Journal,  June  7,  1890)  gave  an  account  of  M. 
Babes' s  researches  on  the  bacillus  of  glanders,  which  show  that  this 
microorganism,  when  obtained  from  pure  cultivations,  can  penetrate 
the  healthy  tissue  of  animals,  and  thus  cause  glanders.  Rubbing 
in  an  ointment  containing  the  bacillus  rarely  succeeds,  and  only 
when  the  virus  is  very  active,  and  obtained  from  a  perfectly  fresh 
cultivation.  M.  Nocard  has  repeated  these  experiments,  and  two 
guinea-pigs  out  of  five  were  infected  by  this  method  of  inoculation. 

Kranzfeld  (Zur  Kenntniss  des  Rotz-bacillus,"  Gentralblatt  fur 
jBakteriologie  und  Parasitenkunde,  Bd.  xi.,  No.  10)  has  recently 
published  the  results  which  he  obtained  by  inoculations  with  the 
virus  of  glanders  in  an  animal  which  had  not  hitherto  been  sub- 
jected to  experimentation  of  this  kind.  He  procured  a  pure  cul- 


GLANDERS    IN    MAX.  211 

ture  from  a  nodule  of  a  man  who  had  died  of  glanders  after  a 
brief  illness.  Inoculations  were  made  in  a  small  rodent  which  is 
very  numerous  in  the  southern  part  of  Russia,  the  spermophilus 
guttatus.  The  course  of  the  disease  in  this  animal  was  almost  the 
same  as  in  the  field  mice  which  were  used  by  Loffler.  Of  twenty- 
eight  animals  infected  with  different  cultures,  sixteen  died  on  the 
fourth  day,  nine  on  the  fifth,  two  on  the  seventh,  and  one  on  the 
tenth.  The  post-mortem  appearances  were  always  characteristic; 
a  greenish-gray  infiltration  at  the  point  of  inoculation,  and  a  num- 
ber of  nodules  in  the  spleen  ;  in  one  animal  also  very  small  white 
nodules  in  the  liver.  Cultivations  from  these  nodules  yielded  a 
pure  growth  of  the  bacillus  of  glanders. 

If  an  animal  is  infected  by  the  direct  injection  of  a  pure  culture 
into  a  vein,  no  serious  symptoms  are  produced,  but  if  soon  there- 
after one  or  more  muscles  are  injured  subcutaneously,  the  microbes 
escape  through  the  lacerated  vessel  sand  localize  at  the  seat  of  injury 
and  produce  a  grave  form  of  the  disease.  It  has  been  found  by 
experiment  that  the  further  from  the  trunk  prophylactic  inocula- 
tions are  made  the  less  intense  is  the  local  reaction.  When  an  ani- 
mal is  inoculated  at  a  distance  from  the  trunk  and  shows  no  gene- 
ral symptoms,  a  subcutaneous  injury  of  any  portion  of  the  trunk 
will  furnish  conditions  for  a  local  form  of  infection. 

GLANDERS  IN  MAN. — The  virus  of  glanders  can  only  find 
entrance  into  the  organism  through  a  wounded  surface.  Whether 
infection  may  not  also  take  place  through  the  alimentary  canal  has 
so  far  not  been  definitely  ascertained.  It  is  certain  that  the  disease 
cannot  be  contracted  by  eating  boiled  or  fried  meat  of  animals 
affected  with  glanders.  Infection  through  the  respiratory  organs 
is  possible,  as  cases  have  been  reported  in  which  the  lungs  were  the 
primary  and  only  seat  of  the  disease.  The  disease  can  also  be 
transmitted  from  the  mother  to  the  foetus  in  utero. 

When  man  is  the  subject  of  glanders,  bacilli  are  found  more  con- 
stantly in  the  blood  than  in  animals.  In  the  case  described  by 
Weichselbaum  numerous  bacilli  could  be  seen  in  the  blood.  In 
this  case  a  thrombus  was  found  in  one  of  the  large  meningeal  veins 
which  contained  numerous  bacilli,  and  which  undoubtedly  was  one 
of  the  sources  of  the  bacilli  in  the  circulation.  In  man  the  nasal 
mucous  membrane  is  not  as  frequently  affected  as  in  animals, 
although  Bellinger  has  shown  that  in  horses  the  nasal  cavity  is  not 
always  affected,  and  that  it  may  present  a  normal  condition  even 
when  the  larynx  and  lungs  are  seriously  affected.  Muscular 
abscesses  which  may  simulate  rheumatism,  are  a  frequent  occur- 
rence, especially  in  the  chronic  form  of  the  disease. 

A  Russian  medical  paper  of  recent  date  (British  Medical  Journal, 
June  11,  1888)  states  that  a  young  soldier,  who  had  been  a  wag- 


212  GLANDERS. 

goner  before  his  admission  into  the  army,  was  received  into  the 
military  hospital  suffering  from  two  foul  ulcers  on  the  hard  palate, 
which  had  perforated  the  nasal  fossa  and  destroyed  the  inferior 
turbinated  bones.  Three  weeks  later  a  swelling  appeared  over  the 
eyebrow  ;  a  fortnight  afterward  he  complained  of  pain  on  the  inner 
side  of  the  left  knee  around  the  internal  tuberosity  of  the  tibia. 
Then  purulent  discharge  occurred  from  the  left  ear,  and  an  abscess 
on  the  back  of  the  right  hand,  which  appeared  as  a  deep  purple 
tubercle,  with  a  hard  circumference,  and  sunken  toward  the  centre ; 
purulent  discharge  oozed  from  the  surface.  At  first,  for  a  short 
time  after  admission,  the  temperature  varied,  rising  of  an  evening 
to  103°  to  104°  ;  later  on,  it  fell  to  normal.  The  disease  was 
mistaken  for  syphilis,  and  iodide  of  potassium  was  given  without 
the  least  benefit.  About  ten  weeks  after  admission  he  was  in  better 
health  and  left  the  hospital,  receiving  his  discharge  from  the  army. 
Within  a  few  weeks  he  returned  with  extension  of  ulceration  of 
the  hard  palate;  the  uvula  was  destroyed.  The  characteristic 
tubercles,  the  "  farcy  buds,"  appeared  in  the  face,  the  metastatic 
abscess  on  the  back  of  the  hand  remained.  The  patient  ultimately 
died  of  exhaustion.  Before  death  some  of  the  tubercles  were 
extirpated  ;  they  were  found  to  contain  microorganisms  resembling 
the  glanders  bacillus  of  Loffler  and  Schlitz. 

Swelling  of  the  testicles  has  also  been  frequently  observed.  In 
other  cases  acute  or  chronic  pulmonary  affections  which  simulate 
pneumonia  or  tuberculosis  are  the  most  important  clinical  features. 
If  the  disease  attacks  the  nasal  cavity,  the  mucous  membrane  pre- 
sents hard  nodules,  and  a  copious  discharge  from  the  nose  is  present. 

Klittner  reports  a  number  of  cases  in  which  the  skin  was  the 
seat  of  numerous  points  of  suppuration  in  the  form  of  pustules  or 
more  diffuse  purulent  processes.  The  pus  found  in  glanders  is 
grayish-red,  and  quite  tenacious  in  recent  lesions,  but  when  suppu- 
ration continues  it  assumes  the  characters  of  ordinary  pus.  An 
acute  and  a  chronic  form  of  glanders  have  been  described,  a  classi- 
fication which  is  accepted  by  Bellinger.  The  bacillus  of  glanders, 
after  localization  in  the  organism,  produces  rapid  tissue-changes 
which  at  first  consist  in  the  formation  of  granulation  tissue,  which, 
when  it  becomes  saturated  with  the  ptomaines  of  the  bacilli,  under- 
goes transformation  into  pus,  a  stage  of  the  disease  which  is  indi- 
cated by  the  formation  of  abscesses  wherever  localization  has  taken 
place,  either  by  direct  infection,  secondary  infection  by  regional 
diffusion  through  the  lymphatic  vessels,  or  by  metastasis  through 
the  systemic  circulation.  The  nodules  in  internal  organs  are  indi- 
cations that  general  infection  has  taken  place  by  embolism. 

In  cases  in  which  no  positive  diagnosis  can  be  made  from  a 
clinical  aspect  it  becomes  necessary  to  resort  to  cultivation  and 
inoculation  experiments. 


CHAPTER    XX. 

ACTINOMYCOSIS  HOMINIS. 

ALTHOUGH  the  parasite  which  is  the  direct  cause  of  this  disease 
is  Dot,  properly  speaking,  a  microorganism,  as  its  presence  in  some 
cases  can  be  detected  by  the  naked  eye,  I  shall  include  it  in  the 
list  of  surgical  diseases  due  to  the  presence  of  microbes,  as  it  often 
requires  the  aid  of  the  microscope  to  make  a  positive  differential 
diagnosis  between  this  and  other  chronic  infectious  diseases  charac- 
terized by  the  presence  of  granulation  tissue. 

HISTORY. — The  disease  as  occurring  in  cattle  was  first  described 
by  Bollinger  ("  Ueber  erne  neue  Pilzkrankheit  beim  Riude," 
Centralblatt  fur  die  medicinischen  Wissenschaften,  No.  27,  1877)  in 
1877,  as  a  condition  in  which  sarcoma-like  tumors  were  met  with, 
associated  with  a  peculiar  growth  which,  from  its  structure,  was 
named  Strahlenpilz  (ray-fungus),  or  actinomyces.  James  Israel 
("  Neue  Beobachtungen  auf  dem  Gebiete  der  Mykosen  des  Men- 
schen," Virchow's  Arehiv,  Bd.  Ixxiv.,  1878)  was  the  first  to  recognize 
the  disease  in  man,  but  it  was  not  generally  understood  until  the 
appearance  of  the  classical  work  of  Ponfick  (Die  Aktinomykose  des 
Menschen,  Berlin,  1882)  in  1882.  Numerous  articles  on  this  sub- 
ject have  since  appeared  in  the  current  medical  literature,  so  that 
Partsch  some  two  years  ago  brought  at  the  end  of  his  mono- 
graph ("  Die  Aktinomykose  des  Menschen  vom  klinischen  Stand- 
pun  kte  besprochen,"  Sammlung  klinischer  Vortrdge,  Nos.  306  and 
307,  1888)  seventy-five  references  with  a  supplemental  list  contain- 
ing thirty-three  names  furnished  by  Schuchardt.  Since  the  publi- 
cation of  Israel's  case  numerous  cases  have  been  reported  by  different 
observers  representing  Germany,  England,  Belgium,  Switzerland, 
Russia,  Austria,  and  America,  so  that  Partsch,  in  the  work  referred 
to  above,  estimates  the  whole  number  at  not  less  than  one  hundred. 

While  most  of  the  articles  in  medical  journals  contain  only  a 
description  of  isolated  cases,  it  appears  to  have  been  the  good  for- 
tune of  some  of  the  writers  on  this  subject  to  meet  with  a  number 
of  cases  in  a  comparatively  short  time.  Thus  Hochenegg  ("  Zur 
Kasuistic  der  Aktinomykose  des  Menschen."  Wiener  med.  Presse, 
Nos.  16  and  18,  1887)  reports  in  his  paper  seven  cases,  and  Moos- 
briigger  ("  Ueber  die  Aktinomykose  des  Menschen,"  Bruins' 
Beitrdge  zur  klinischen  Chirurgie,  Bd.  ii.  Heft.  2,  S.  339,  Tiibin- 


21-i  ACTING  MYCOSIS    HO  MINIS. 

gen,  1886)  has  increased  the  statistics  by  ten  well -authenticated  and 
carefully  recorded  cases.  At  the  last  meeting  of  the  Versarnmlung 
Deutscher  Naturforscher  und  Aerzte,  Kotter  stated  that  he  observed 
thirteen  cases  in  two  years.  Albert  has  seen  not  less  than  thirty- 
eight  cases  of  actinomycosis  within  the  past  few  years  ;  of  these 
eight  have  come  under  his  observation  during  the  last  year.  These 
cases  have  come  mostly  from  Vienna  and  its  vicinity. 

DESCRIPTION  OF  FUNGUS. — Bollinger  described  as  peculiar! to 
this  disease  certain  yellowish  bodies,  visible  to  the  naked  eye,  which 
were  always  found  in  the  pus  of  abscesses  and  in  the  middle  of  the 
tumors.  Microscopically  they  were  found  to  consist  of  threads 
similar  to  the  ordinary  mycelium,  which  terminated  in  bulbous 
ends.  The  threads  radiate  from  the  centre,  and  their  clubbed 
extremities  impart  to  the  fungus  the  characteristic  ray-like  appear- 
ance (Fig.  8).  Sometimes  but  one  of  these  bulbs  is  connected  with 


FIG. 


Three  actinomyces  from  a  case  of  pulmonary  actinomycosis.     Below,  three  finger- 
like  buds  and  dichomatous  branching  of  actinomyces  threads.    X  450.    (BAUMGARTEN.) 

a  thread,  at  other  times  there  may  be  several.  In  man  the  actino- 
myces occurs  as  small  globular  masses,  commonly  about  the  size  of 
a  millet-seed,  usually  of  a  pale  yellow  color,  but  at  times  white, 
brown,  green,  or  speckled,  the  color  being  influenced  by  age  and 
the  consecutive  pathological  conditions  by  which  it  may  be  sur- 
rounded. In  man  the  clubbed  bodies  are  commonly  absent,  and 
the  growth  consists  of  the  radiating  filaments  alone.  The  rays, 
when  immersed  in  water  or  in  a  weak  solution  of  chloride  of  sodium, 
become  enormously  swollen  and  lose  their  shape,  while  they  effectu- 
ally resist  the  action  of  acids,  ether,  and  chloroform.  For  staining 
actinomyces  Weigert  uses  WedPs  orseille,  Marchand  eosin,  Dunker 
and  Maguussen  cochineal-red,  Moosbriigger  hsematoxylou-alum, 
and  Partsch,  in  section-staining,  has  had  the  best  results  with 


CULTIVATION    EXPERIMENTS.  215 

Gram's  method.  Recently  Babes  has  made  beautiful  dry  prepara- 
tions by  using  a  two  per  cent,  solution  of  safrauiu  in  aniline  oil, 
followed  by  treatment  with  iodide  of  potassium.  O.  Israel  "Ueber 
Doppelfarbung  mit  Orceiu,"  Yirchow's  Archiv,  Bd.  105,  S.  169) 
has  found  that  a  solution  of  orcein  in  acetic  acid  stains  the  rays  a 
Bordeaux-red,  while  the  filaments,  if  decolorization  is  not  carried 
too  far,  present  a  blue  tinge.  Baranski  (Deutsche  med.  Wochen- 
schrift,  1887)  uses  picrocarmine  for  staining  fresh  preparations  of 
actiuomyces  bovis.  A  small  amount  of  the  contents  of  a  yellow 
nodule,  or  pus  from  the  part,  is  spread  in  a  thin  layer  on  a  cover- 
glass,  and  dried  in  the  air.  The  cover  is  then  passed  three  times 
through  the  flame  of  an  alcohol  lamp,  care  being  taken  not  to  over- 
heat the  preparation.  It  is  then  floated  in  the  picrocarmiue  solu- 
tion, or  a  few  drops  of  the  staining  fluid  are  placed  on  the  cover. 
The  staining  is  finished  in  two  or  three  minutes.  The  cover  is 
then  carefully  washed  by  agitating  it  in  distilled  water  and  alcohol, 
and  examined  in  water  and  glycerin.  The  fungus  takes  a  yelk/w 
color,  while  the  remaining  structure  appears  red.  As  regards  the 
history  of  the  parasite  outside  the  body,  as  yet  only  a  few  facts  are 
known.  It  is  found  in  pig's  meat  and  is  peculiarly  susceptible  to 
outside  influences.  It  cannot  be  cultivated  in  pure  water  or  one- 
half  per  cent,  solution  of  salt,  such  as  is  usually  employed  for 
similar  forms,  as  in  these  elements  the  fungi  swell  up  and  assume 
fantastic  shapes.  Yirchow  found  them  as  small  calcareous  con- 
cretions in  the  muscle  fibres  of  the  pig,  and  considered  their  flesh 
highly  dangerous  food,  unless  well  cooked. 

CULTIVATION  EXPERIMENTS. — It  has  been  found  extremely 
difficult  to  cultivate  the  actinomyces,  probably  on  account  of  the 
usual  culture  media  not  being  well  adapted  for  its  growth.  The 
first  successful  experiments  were  made  by  Bostrom  (Jahresbericht 
uber  pathologische  Anatomie,  Baumgarten,  1886),  of  Giessen,  upon 
plates  of  blood  serum  and  agar-agar,  the  fungus  attaining  its  ma- 
turity in  five  or  six  days,  when  it  presented  the  typical  appearances 
of  actinomyces  as  found  in  man.  0.  Israel  ("Ueber  die  Cultivir- 
barkheit  des  Actinomyces,"  Yirchow's  Archiv,  B.  95,  Heft  1)  cul- 
tivated the  fungus  successfully  upon  coagulated  blood  serum.  The 
culture  grows  very  slowly,  and  the  fungus  often  undergoes  calcifica- 
tion. He  made  the  observation  that  water,  glycerin,  blood  serum, 
and  weak  saline  solutions  seriously  impair  the  vitality  of  the  fungus, 
and  believes  that  the  effect  of  these  agents  on  the  actinomyces 
explains  the  failure  of  previous  culture  and  inoculation  experiments. 
Until  recently,  coagulated  blood  serum  is  the  only  medium  upon 
which  the  fungus  has  been  successfully  cultivated.  If  evaporation 
is  prevented,  a  thin  velvety  layer  forms  on  the  surface  of  the  blood 
serum  in  about  eight  weeks,  in  the  vicinity  of  which,  not  before  the 


216  ACTINOMYCOSIS    HOMINIS, 

expiration  of  fourteen  days,  the  growth  appears  more  in  a  down- 
ward direction  than  on  the  sides  of  the  inoculation  puncture.  From 
the  tenth  to  the  fourteenth  day  numerous  spores  are  produced,  and 
a  thick  wall  of  club-shaped  mycelia  in  typical  centrifugal  arrange- 
ment. 

At  a  meeting  of  the  Medical  Society  of  Berlin,  March  5,  1890 
(Berliner  Minische  Wochenschrift,  March  31,  1890),  M.  Wolf  made 
a  communication  in  which  he  described  culture  experiments  which 
he  and  Israel  made  with  actiuomyces.  He  announced  that  they 
had  succeeded  in  cultivating  the  actinomyces  in  and  upon  egg  and 
agar-agar.  The  inoculations  were  made  from  a  case  of  retro-max- 
illary actinomycosis  immediately  after  the  abscess  was  incised. 
With  the  yellow  granules,  deep  and  superficial,  inoculations  were 
made  in  agar-agar.  It  was  found  that  the  actinomyces  is  not  an 
anaerobic  fungus,  as  it  grew  upon  the  surface  as  well  as  in  the  depth 
of  the  culture  soil.  The  agar  culture  appeared  first  as  transparent 
little  drops  which,  by  confluence,  made  an  opaque  white  mass. 
Under  the  microscope  the  culture  was  seen  to  be  composed  of  short 
thick  rods,  with  an  admixture  of  other  elements.  The  egg  cultures, 
on  the  other  hand,  were  made  up  of  the  short  thick  rods,  besides  a 
mass  of  threads,  some  of  them  twisted  in  the  shape  of  a  corkscrew, 
presenting  an  intricate  network  of  threads.  Three  rabbits  were 
inoculated  by  implantation  of  the  pure  culture  into  the  peritoneal 
cavity.  The  post-mortem  showed  numerous  nodules  upon  the  pa- 
rietal peritoneum,  the  omentum,  and  between  the  intestines,  the  size 
of  a  pin's  head  to  that  of  a  hazelnut,  surrounded  by  a  fibrous  cap- 
sule. The  interior  of  these  nodules  was  composed  of  a  yellow  mass 
the  consistence  of  tallow.  In  these  nodules  typical  actiuomyces 
were  found  imbedded  in  masses  of  round  cells  in  a  state  of  fatty 
degeneration. 

INOCULATION  EXPERIMENTS.  —  James  Israel  ("  Erfolgreiche 
Uebertragung  der  Aktinomykose  des  Menschen  auf  das  Kanin- 
chen,"  Centralblatt  fur  die  med.  Wissenschqften,  1883,  No.  27)  was 
successful  in  inoculating  a  rabbit  from  man  by  introducing  a  mass 
of  granulation  tissue  into  the  peritoneal  cavity,  and  Poufick  pro- 
duced the  disease  in  calves  by  implantation  of  a  portion  of  the 
granulation  mass  into  the  subcutaneous  tissue,  the  abdominal  cavity, 
or  into  veins.  Rotter  (Centralblatt /.  Bakteriologie  und  Parasiten- 
kunde,  B.  lii.  No.  14,  1888)  experimented  on  calves,  pigs,  dogs, 
guinea-pigs,  and  rabbits,  and  in  only  one  instance,  a  rabbit,  did  he 
succeed  in  reproducing  the  disease.  In  this  instance  a  piece  of 
granulation  tissue,  the  size  of  a  beau,  was  inserted  into  the  peri- 
toneal cavity,  and  the  animal,  having  manifested  no  symptoms  of 
disease,  was  killed  six  months  after  the  inoculation.  On  opening 
the  abdominal  cavity  about  twenty  nodules,  varying  in  size  from 


EFFECT    OF    ACTINOMYCES    ON    THE    TISSUES.       217 

the  head  of  a  pin  to  a  hazeluut  were  found  distributed  over  a  con- 
siderable surface,  each  of  them  showing  the  typical  histological 
structure  of  actinomycosis.  The  transplanted  piece  of  tissue  was 
found  perfectly  encapsulated  in  one  of  the  nodules  the  size  of  a  bean. 
As  the  fungus  was  found  in  all  the  nodules  it  is  only  reasonable  to 
conclude  that  the  disease  spread  from  the  original  depot  by  migra- 
tion of  some  of  the  new  fungi,  which  at  their  respective  points  of 
localization  established  independent  centres  of  infection  and  tissue 
proliferation.  While  the  actinomyces  in  the  new  nodules  presented  a 
perfect  structure,  and  could  be  readily  stained,  the  transplanted 
fungus  in  the  graft  had  lost  its  structure,  and  could  no  longer  be 
stained. 

SOURCES  OF  INFECTION. — As  the  actiuomyces  found  in  man  and 
beast  resemble  each  other  morphologically,  and  in  their  effect  on 
the  tissues,  as  well  as  in  their  reaction  to  chemical  substances,  it  is 
evident  that  the  etiology  of  the  disease  is  similar  in  both  of  them. 
The  fungus  has  never  been  found  outside  of  the  body.  Israel  is  of 
the  opinion  that  both  man  and  animals  are  infected  from  the  same 
source,  such  as  vegetables  or  water.  Jensen  (Tidskrift  f.  Vderincir, 
B.  xiii.,  1883)  traced  an  epidemic  in  Seeland  to  the  eating  of  rye 
grown  on  laud  recently  reclaimed  from  the  sea;  and  Johne  dis- 
covered a  fungus  closely  resembling  the  actinomyces  in  grains  of 
rye  stuck  in  the  tonsils  of  pigs.  That  the  ears  of  barley  or  rye  are 
sometimes  the  carriers  of  the  coutagium  is  well  illustrated  by  the 
case  reported  by  Soltmanu  ("  Ueber  Aetiologie  und  Ausbreitungs- 
bezirk  der  Aktinomykose,"  Jahrbuch  f.  Kinder  heilkunde,  B.  xxiv. 
p.  129).  The  patient  was  a  boy,  who  had  swallowed  an  ear  of 
barley.  The  foreign  body  lodged  in  the  pharynx,  where  it  gave 
rise  to  difficulty  in  deglutition  ;  afterward  it  perforated  the  pharyn- 
geal  wall,  an  accident  which  was  attended  by  hemorrhage;  and 
later  an  actinomycotic  phlegmon  developed,  which  spread  rapidly, 
and  finally  opened  below  the  scapula.  Through  this  opening  the 
foreign  body  was  extracted.  Piaua  (Virchow  u.  Hirsch's  Jahres- 
bericht,  1887,  B.  i.  p.  293)  examined  the  tongue  of  a  cow  suffering 
from  a  circumscribed  actiuomycosis,  in  which  the  disease  could  be 
traced  to  a  similar  origin — perforation  of  the  tissues  and  infection 
by  a  sharp  beard  of  the  ear  of  barley.  Actinomycosis  has  as  yet 
only  been  found  amongst  herbivorous  and  omnivorous  animals, 
including  man,  and  the  frequent  location  of  the  primary  swelling 
in  the  mouth  seems  to  indicate  that  the  fungus  gains  entrance  with 
food. 

EFFECT  OF  ACTINOMYCES  ON  THE  TISSUES. — As  to  the  manner 
in  which  the  fungus  exerts  its  pathogenic  action  much  yet  remains 
to  be  ascertained.  The  most  striking  effect  is  the  transformation 
of  mature  connective  tissue  into  embryonal  or  granulation  tissue. 


2L8  ACTINOMYCOSIS     HOMINIS. 

The  product  of  inflammation  around  each  fungus  consists  of  granu- 
lation tissue,  which  resembles  tubercle  tissue.  At  first  the  cells  are 
round,  at  a  later  stage  of  the  inflammation  epithelioid  and  giant 
cells  are  formed  immediately  around  the  fungus.  As  the  disease 
is  almost  always  attended  by  suppuration  at  some  time  during  its 
course,  it  has  been  customary  to  ascribe  to  the  actinomyces  pyogenic 
properties.  Israel  has  always  held  that  the  actinomyces  is  a  pus- 
producing  fungus,  in  opposition  to  Ponfick  and  some  other  patholo- 
gists,  who  claim  that  when  suppuration  takes  place  it  is  the  result 
of  a  secondary  infection  with  pus-microbes.  As  cases  of  actinomy- 
cosis  have  been  reported  which  remained  stationary  in  the  granula- 
tion stage  for  an  indefinite  time  without  suppuration  taking  place, 
and  pus-microbes  have  been  cultivated  from  the  pus  of  actinomy- 
cotic  abscesses,  it  appears  more  than  probable  that  suppuration 
occurred  independently  of  the  presence  of  the  fungus,  and  was  pro- 
duced by  the  specific  action  of  pus-microbes  on  the  granulation 
tissue.  Firket  (Revue  de  Mgdecine,  1884)  asserts  that  the  actino- 
myces does  not  appear  to  produce  u  coagulation-necrosis/'  but  from 
a  study  of  the  earliest  formed  colonies  he  finds  that  the  first  eifect 
of  the  fungus  is  to  induce  cellular  hyperplasia.  It  is  as  if  the  tissue 
elements  resented  the  intrusion  of  the  parasite,  which,  however, 
mostly  gains  the  upper  hand,  so  that  the  result  is  the  formation  of 
granulation  tissue,  and,  later,  abscesses  that  characterize  the  disease. 
As  a  rule,  it  may  be  stated  that  the  earlier  suppuration  takes  place 
the  more  rapid  the  spread  of  the  disease  and  the  graver  the  prog- 
nosis, while  the  absence  of  suppuration  indicates  comparative  be- 
nignancy,  and  points  in  the  direction  of  a  more  chronic  form  of  the 
affection.  The  localized  chronic  form  of  actinomycosis  resembles 
in  its  clinical  features  and  its  anatomical  locations  more  closely 
sarcoma  than  any  other  affection.  In  such  cases  it  would  be  diffi- 
cult, if  not  impossible,  in  the  absence  of  the  specific  fungus,  to  make 
a  differential  diagnosis  between  it  and  round-celled  sarcoma,  even 
by  a  most  careful  microscopical  examination,  as  the  histological 
structure  of  both  is  almost  identical. 

CLINICAL  HISTORY. — Usually  the  disease  follows  quite  a 
chronic  course  and  the  swelling  at  the  seat  of  primary  localization 
resembles  in  its  clinical  history  more  a  tumor  than  an  inflammatory 
swelling.  The  extension  of  the  morbid  process  takes  place  by  dif- 
fusion of  the  actinomyces  in  loco,  in  preference  along  the  loose 
connective-tissue  spaces,  each  fungus  constituting  a  nucleus  for  a 
nodule  of  granulation  tissue.  By  confluence  of  many  such  nodules 
the  inflammatory  swelling  often  attains  a  very  large  size,  and  when 
suppuration  occurs  in  the  interior  the  further  history  is  that  of 
abscess.  Diffusion  never  takes  place  along  the  course  of  lymphatic 
vessels  and  glands.  When  these  structures  are  affected  in  the 


SEAT    OF    PRIMAEY     INVASION.  219 

course  of  the  disease,  they  indicate  that  secondary  infection  has 
taken  place.  In  some  instances  the  disease  pursues  such  a  rapid 
course  that  it  may  be  mistaken  for  an  acute  phlegmonous  inflam- 
mation, osteomyelitis,  or,  when  diffused  over  a  large  surface  of  the 
body,  for  syphilis.  A  good  illustration  of  the  former  class  is  fur- 
nished by  the  case  reported  by  Kapper  ("  Ein  Fall  von  acuter 
Aktinomykose,"  Wiener  med.  Presse,  No.  3,  1887).  A  soldier, 
twenty-two  years  of  age,  became  suddenly  ill  with  febrile  symp- 
toms and  a  rapidly  increasing  swelling  of  the  lower  jaw.  An  early 
incision  was  made  and  liberated  a  large  quantity  of  pus,  which,  on 
microscopical  examination,  was  found  to  contain  actinomyces.  It 
is  interesting  to  note  that  in  this  case  the  carious  teeth,  from  where 
the  infection  had  evidently  taken  place,  contained  threads  of  lepto- 
thrix  and  actiuomyces.  At  a  meeting  of  the  Berlin  Medical 
Society,  O.  Israel  (Berliner  Ein.  Wochenschrift,  Jan.  23,  1888)  gave 
an  accurate  description  of  the  post-mortem  appearances  of  a  case  of 
diffuse  actinomycosis.  The  patient,  a  woman,  forty- four  years  of 
age,  had  been  treated  for  syphilis  in  one  of  the  surgical  clinics. 
The  heart  contained  a  number  of  minute  abscesses  in  which  the 
fungus  could  be  found  in  large  numbers.  A  large  abscess  between 
the  diaphragm,  stomach,  and  spleen  contained  thick  pus  of  a 
greenish  color,  an  unusual  occurrence  in  cases  of  actinomycosis,  but 
no  actinomyces.  The  spleen  was  the  seat  of  a  large  and  of  numerous 
minute  abscesses,  and  the  liver  and  kidneys  also  contained  small 
abscesses,  and  in  all  of  them  actinomyces  could  be  found.  Israel 
claims  that  this  case  furnishes  a  good  illustration  of  his  views,  that 
the  actinomyces,  as  regards  its  effect  on  the  tissues,  occupies  a  posi- 
tion half-way  between  the  bacillus  of  tuberculosis,  which  produces 
only  granulation  tissue,  and  the  pus-microbes,  which  produce  pus. 
It  was  impossible  in  this  case,  as  in  so  many  others  in  which  mul- 
tiple deposits  have  been  found,  to  locate  the  primary  seat  of  infec- 
tion. The  teeth  were  perfect  and  the  whole  digestive  tract  showed 
no  evidences  of  disease. 

SEAT  OF  PRIMARY  INVASION. — If  infection  takes  place  by  fully 
developed  actinomyces,  it  can  only  do  so  by  the  fungus  gaining 
entrance  into  the  tissue  through  some  loss  of  continuity  in  the 
cutaneous  or  mucous  surface,  as  any  other  method  of  ingress  is 
impossible  on  account  of  the  large  size  of  the  fungus,  in  the  cases 
in  which  no  such  primary  infection-atrium  could  be  found,  it  must 
be  taken  for  granted  that  the  local  lesion  had  healed  between  the 
time  infection  took  place  and  the  first  manifestations  of  the  disease, 
or  that  infection  was  caused  by  the  entrance  of  spores,  which  from 
their  smaller  size  could  find  their  way  into  the  tissue  through  intact 
mucous  surfaces.  In  reference  to  the  primary  localization  of  the 
disease,  Moosbrugger  gives  the  following  statistics  :  In  29  cases  the 


220  ACTIXO  MYCOSIS     HO  MINIS. 

lower  jaw,  mouth,  and  throat  were  affected  ;  in  9  the  upper  jaw 
and  cheek  ;  in  1  the  tongue ;  in  2  the  region  of  the  oesophagus  ;  in 
11  the  intestines ;  in  14  the  bronchial  tract  and  the  lungs ;  in  7  the 
point  of  entrance  could  not  be  ascertained.  lufectiou  may  take 
place  through  any  abraded  surface  brought  in  contact  with  the 
specific  cause,  aud  for  clinical  purposes  the  cases  can  be  divided 
into  the  following  three  groups :  1.  Cutaneous  surface.  2.  Ali- 
mentary canal.  3.  Kespiratory  tract. 

1.  Cutaneous  surface.  Partsch  (Deutsche  Zeitschrifif.  Chirurgie, 
B.  23,  p.  498)  describes  a  case  of  actinomvcosis  in  which  the  dis- 
ease developed  in  the  scar  left  after  extirpation  of  the  breast.  The 
patient  was  a  man,  aged  sixty.  In  June,  1884,  his  left  breast  was 
removed  for  an  ulcerating  carcinoma.  As  the  wound  did  not  heal 
by  primary  union  and  the  process  of  cicatrization  was  very  slow,  a 
number  of  small  skin-grafts,  from  a  perfectly  healthy  young  man, 
were  transplanted.  The  wound  was  practically  healed  in  Septem- 
ber. Two  months  later,  the  cicatrix  ulcerated  and  an  abscess  dis- 
charged itself.  Actinomyces  were  found  in  the  pus.  The  parts 
were  excised,  and  the  progress  of  the  disease  was  apparently  arrested. 
No  explanation  could  be  made  how  the  infection  occurred. 

Hochenegg  reported  a  case  of  actiuomycosis  of  the  skin  of  the 
left  submaxillary  region,  in  which  he  attributed  the  disease  to  an 
invasion  of  the  fungus  through  a  small  atheroma. 

Kaposi  (Wiener  med.  Wochenschrift,  Nos.  19-22,  1887)  reports 
a  very  chronic  case  of  actinomycosis  which  primarily  started  in  the 
skin.  When  first  noticed,  it  appeared  as  a  red  spot  the  size  of  a 
florin  on  the  left  pectoral  muscle,  which  gradually  increased  to  the 
size  of  a  walnut,  and  then  gradually  flattened  down  and  disap- 
peared. Meanwhile  fresh  spots  and  lumps  appeared,  some  as  large 
as  a  pigeon's  egg.  Eleven  years  after  the  beginning  of  the  disease 
a  swelling  as  large  as  an  apple  appeared  over  the  spine  of  the  sixth 
vertebra,  which  gradually  extended  forward  and  a  year  later  formed 
a  large  swelling  behind  the  right  axilla.  A  year  later,  this  swell- 
ing had  diminished  in  size  to  that  of  a  pigeon's  egg,  and  then  again 
increased  in  size.  Ulceration  set  in,  exposing  a  fungous  bleeding 
surface.  At  this  time  the  entire  trunk,  but  not  the  limbs,  was 
covered  with  nodules,  spots,  and  stripes.  The  swellings  were 
heaped  in  masses.  The  infiltration  was  located  in  the  corium.  In 
this  case  it  appears  that  secondary  infection  with  pus-microbes 
only  occurred  at  the  points  of  ulceration. 

At  the  meeting  of  the  German  Society  of  Surgeons  in  1889, 
Leser  (Klinisclier  Beitrag  zur  Aktinomykose  des  Menschen)  reported 
three  cases  of  primary  actinomycosis  of  the  skin  which  had  come 
under  his  own  observation  in  the  course  of  a  single  year.  In  his 
remarks  on  this  subject  he  placed  special  stress  on  the  manner  in 


SEAT    OF    PRIMARY    INVASION.  221 

which  the  disease  extends.  In  the  periphery  of  the  primary  lesion 
he  found  numerous  nodules  which  later  became  the  seat  of  destruc- 
tive changes,  resembling  in  this  respect  the  clinical  features  of  tuber- 
culosis of  the  skin.  The  extension  of  the  disease  in  the  direction 
of  the  deep  tissues  takes  place  by  the  formation  of  passages  the  cir- 
cumference of  which  corresponds  to  the  size  of  a  lead-pencil ;  these 
are  filled  with  yellowish-gray  or  reddish-gray  granulations  which 
attack  and  destroy  tissues  irrespective  of  their  anatomical  structure. 
The  lymphatic  glands  were  always  found  intact. 

2.  Alimentary  canal.  The  frequency  with  which  the  disease 
aifects  the  mouth  and  jaws  of  cattle  is  explained  by  the  occurrence 
of  numerous  points  of  injury  caused  by  the  chewing  of  rough  food, 
which  furnish  the  necessary  infection-atrium  through  which  the 
fungus  enters  the  tissues. 

a.  Teeth.  In  man  infection  takes  place  frequently  through 
carious  teeth  and  through  abrasions  in  the  tongue  and  mucous 
membrane  of  the  mouth. 

Israel  (Klinische  Beitrage  zur  Kenntniss  der  Aldinomykose  des 
Menschen,  Berlin,  1885)  found  the  fungus  in  the  cavities  of  carious 
teeth,  and  Partsch  found,  in  the  same  locality,  almost  pure  cultures 
without  any  manifestations  of  disease  except  chronic  periodontitis. 
The  fungus  occurs  here  often  side  by  side  with  leptothrix. 

b.  Tongue.     Hochenegg   saw  a  case  of  actinomycosis   of  the 
tongue  caused  by  an  infected  carious  tooth.     The  swelling  was  the 
size  of  a  cherry  located  near  the  apex  of  the  organ.     The  aifectiou 
had  existed  for  two   months.     The  growth  was  excised,  and  on 
examination  was  found  to   consist  of  granulation   tissue   with    a 
central   yellow  mass  the  size  of  a  millet-seed.     Beside  this   case 
only  three  cases  of  actinomycosis  of  the  tongue  are  on  record ;  one 
primary,  one  secondary  to  disease  of  the  jaw,  and  one  metastatic. 

c.  Jaws.     That  carious  teeth  furnish  a  frequent  infection-atrium 
in  maxillary  actinomycosis  is  well  known,  and  in  many  instances 
the  disease  in  its  early  stages  has  been  mistaken  for  an  ordinary 
dental  affection,  and  patients  have  often  sought  relief  at  the  hands 
of    a   dentist.     The    lower  jaw    is   most   frequently  affected,  the 
growth  being  connected  with  the  bone,  or  situated  close  to  it,  or  it 
has  already  extended  to  the  submental  orsubmaxillary  region.     As 
soon  as  the  loose  tissues  of  the  neck  are  reached,  rapid  extension 
takes  place  in  a  downward  direction  along  the  inter-muscular  septa. 
Israel  refers  to  a  case  in  which  an  actinomycotic  swelling  in  the 
submaxillary   region    extended,  from    the    month    of    August    to 
December,  to  the  level  of  the  thyroid  cartilage.     When  the  disease 
is  primarily  located  in  the  upper  jaw,  which,  however,  occurs  only 
in  exceptional  cases,  it  tends  to  invade  rapidly  the  adjacent  soft 
parts,  and  even  to  implicate  the  base  of  the  skull  and  the  brain. 


222  ACTING  MYCOSIS    HO  MINIS. 

The  prognosis  is  always  more  serious  when  the  disease  aftects  the 
upper  than  the  lower  jaw,  as  the  tendency  here  to  invade  the  deep 
structures  is  much  greater. 

Two  cases  of  actiuomycosis  in  man  have  come  under  my  obser- 
vation, and  as  both  of  them  originated  in  the  mouth  and  represent 
from  a  prognostic  point  two  distinct  classes,  I  will  describe  them 
briefly. 

CASE  I. — This  patient  was  a  man,  thirty  years  of  age,  German  by 
birth,  and  a  soda-water  manufacturer  by  occupation.  His  business 
required  him  to  make  frequent  trips  into  the  country  by  team.  He 
had  no  recollection  of  having  come  in  contact  with  cattle  suffering 
from  "swelled  head"  or  lumpy  jaw.  During  the  winter  of  1886  he 
suffered  from  what  he  supposed  was  an  ordinary  cold  :  the  right  side 
of  the  lower  jaw  was  swollen  and  painful.  As  one  of  the  molar  teeth 
showed  evidences  of  decay  and  had  become  loose  it  was  extracted, 
The  pain  and  swelling,  however,  did  not  improve,  and  the  attending 
physician  extracted  all  of  the  molar  teeth  of  the  lower  jaw.  At  this 
time  a  fungous  mass  commenced  to  appear  over  the  surface  of  the 
edentulous  bone.  The  cheek  on  the  affected  side  was  also  greatly 
swollen.  The  patient  was  admitted  into  the  Milwaukee  Hospital 
about  six  months  after  the  first  symptoms  had  showed  themselves.  At 
this  time  the  lower  jaw,  in  the  mouth,  presented  a  fungous  mass 
extending  from  the  angle  of  the  bone  to  the  first  bicuspid ;  the  swell- 
ing extended  as  far  as  the  tonsils.  The  cheek  was  enormously  swol- 
len from  the  angle  of  the  mouth  to  the  lower  margin  of  the 
parotid  gland.  The  skin  over  the  swollen  part  presented  a  glossy 
appearance,  and  the  superficial  veins  were  considerably  dilated. 
Around  the  margin  of  the  swelling  no  distinct  border-line  could  be  felt, 
the  infiltrated  parts  fading  gradually  into  the  healthy  surrounding 
tissues.  Free  suppuration  from  the  surface  of  the  fungous  granu- 
lations, and  a  number  of  small  abscesses  had  discharged  themselves 
into  the  cavity  of  the  mouth.  As  some  doubt  existed  as  to  the  char- 
acter of  the  inflammation,  careful  and  repeated  examinations  were 
made  of  the  pus  removed  from  the  small  abscess  cavities,  and  on  seve- 
ral occasions  fragments  of  actiuomyces  were  found.  The  discovery  of 
the  specific  cause  of  the  inflammation  cleared  up  the  diagnosis  and 
furnished  a  strong  indication  for  operative  treatment.  An  incision  was 
made  along  the  lower  border  of  the  jaw,  from  just  below  the  articula- 
tion to  near  the  symphysis,  and  after  arresting  all  hemorrhage  it  was 
carried  into  the  cavity  of  the  mouth.  The  alveolar  processes  of  the 
jaw  were  affected  and  were  removed  ;  wherever  the  periosteum  showed 
signs  of  infiltration  it  was  carefully  scraped  away,  and  finally  the  whole 
exposed  bone  surface  was  thoroughly  cauterized.  The  infiltrated  soft 
tissues  were  dissected  out  with  knife  and  scissors,  the  deepest  portions 
extending  as  far  as  the  tonsil.  The  deep  portion  of  the  wound  was 
dusted  over  with  iodoform  and  filled  with  iodoform  gauze,  while  the 
external  wound  was  sutured.  The  entire  external  wound  healed  by 


SEAT    OF    PRIMARY    INVASION.  223 

primary  union,  and  the  cavity  in  the  mouth  closed  slowly  by  granula- 
tion. The  patient's  general  health  improved  rapidly  until  six  weeks 
after  the  operation,  when  the  neck  below  the  scar  became  swollen, 
followed  in  a  short  time  by  the  formation  of  abscesses  reaching  from 
the  angle  of  the  jaw  to  the  clavicle,  and  posteriorly  as  far  as  the  spine 
of  the  scapula.  Numerous  openings  were  made  and  efficient  drain- 
age established,  but  suppuration  continued  and  the  patient  became 
extremely  emaciated.  The  suppurative  process  extended,  and  four 
months  after  the  first  operation  the  patient  died,  the  symptoms  during 
the  last  days  of  life  pointing  to  a  hypostatic  pneumonia.  Actinomyces 
were  constantly  found  in  the  pus  during  the  entire  course  of  the  disease. 
I  believe  that  the  recurrence  of  the  disease  after  operation  was  due  to 
an  imperfect  removal  of  infected  tissues  in  the  posterior  and  lower 
portion  of  the  pharynx. 

CASE  II. — This  case  came  under  my  care  during  the  summer  of 
1887.  Patient  was  a  young  man  who  was  employed  on  a  farm.  About 
five  months  before  he  was  admitted  into  the  Milwaukee  Hospital  he 
had  a  number  of  teeth  extracted  from  the  right  upper  jaw  under  the 
belief  that  the  teeth,  some  of  which  were  decayed,  were  the  cause  of 
the  pain  and  swelling  in  that  region.  The  physician  in  attendance 
diagnosticated  sarcoma  of  the  upper  jaw,  and  sent  the  case  to  me  for 
operation.  On  my  first  examination  1  found  a  swelling  involving  the 
right  side  of  the  face,  extending  from  the  zygomatic  arch  to  near  the 
lower  border  of  the  lower  jaw,  involving  the  deep  tissues  and  being 
connected  with  the  alveolar  processes  of  the  posterior  portion  of  the 
upper  jaw.  The  swelling  was  firm,  and  without  well-defined  margins. 
No  evidences  of  suppuration.  The  history  of  the  case,  and  particularly 
the  location,  extent,  and  physical  properties  of  the  swelling,  led  me  to 
the  opinion  that  it  was  the  result  of  actinomycotic  infection.  All 
infected  tissue  was  thoroughly  excised  through  a  large  external  inci- 
sion, the  jaw-bone  scraped  and  cauterized.  The  entire  thickness  of  the 
cheek,  with  the  exception  of  the  skin  and  superficial  fascia,  appeared 
to  be  transformed  into  granulation  tissue.  In  the  granulations  numer- 
ous yellow  seed-like  bodies  were  found,  which  under  the  microscope 
showed  the  typical  structure  of  the  ray-fungus.  The  mycelia  were 
not  as  bulbous  as  we  find  them  pictured  in  the  books,  but  the  distal 
extremity  appeared  to  be  surrounded  by  dust-like  bodies  presenting 
the  appearance  of  a  small  brush.  Some  of  the  mycelia  appeared  to  be 
more  covered  than  others.  These  minute  bodies  I  looked  upon  as 
spores.  In  the  first  case  in  which  suppuration  had  taken  place  I  never 
succeeded  in  finding  the  actinomyces  perfect  and  complete ;  in  the 
second  case  suppuration  had  not  taken  place,  and  the  fungus  always  was 
found  in  a  perfect  state  and  in  a  condition  of  spore-production.  These 
cases  present  a  striking  contrast  both  in  regard  to  the  local  conditions 
and  the  ultimate  termination.  In  the  first  case  a  secondary  infection 
had  already  taken  place,  and  the  phlegmonous  inflammation  induced 
by  the  pus-microbes  prepared  the  tissues  again  for  the  diffusion  of  the 
actinomycotic  process ;  while  in  the  second  case  the  process  had  not 


224:  ACTINOMYCOSIS    HOMINIS. 

passed  beyond  the  stage  of  granulation,  presenting  a  more  distinct 
boundary-line  between  healthy  and  diseased  tissues,  a  most  important 
factor  in  the  operative  treatment.  The  first  case  died  from  a  recur- 
rence of  the  disease  in  the  vicinity  of  the  operation  wound  and  exten- 
sion to  the  neck  and  chest,  while  in  the  second  case  the  wound  healed 
and  the  patient  has  since  remained  in  perfect  health. 

fl.  Intestines.  In  primary  intestinal  actinomycosis  the  disease 
must  be  due  to  mural  implantation  of  the  fungus  and  infiltration 
of  the  tissues  by  its  progressive  growth.  Arrest  and  implantation 
of  the  actinornyces  are  determined  by  antecedent  pathological 
changes. 

Chiari  ("  Ueber  primare  Darmaktinomykose  des  Menschen," 
Prager  med.  Wochenschrift,  No.  10,  1884)  described  the  post-mor- 
tem appearances  in  a  case  of  primary  intestinal  actinomycosis.  The 
patient  was  a  man  thirty-six  years  of  age,  the  most  prominent 
symptom  being  progressive  marasmus.  At  the  necropsy  chronic 
tuberculosis  in  the  apices  of  the  lungs  and  a  few  tuberculous  ulcer- 
ations  in  the  lower  portion  of  the  ileum  were  found.  The  large 
intestine  presented  a  very  remarkable  appearance,  the  mucous 
membrane  of  which,  except  the  csecum  and  ascending  colon,  was 
covered  with  whitish  deposits,  forming  round  and  oblong  patches 
some  of  them  one  cubic  centimetre  in  diameter,  and  five  milli- 
metres in  thickness.  In  some  of  these  patches  could  be  seen 
minute  yellowish-brown  and  yellowish-green  granules.  The 
patches  were  firmly  adherent  and  when  removed  left  a  loss  of  sub- 
stance in  the  mucous  membrane.  The  mucous  membrane  through- 
out was  in  a  state  of  catarrhal  inflammation.  On  microscopical 
examination  the  granules  proved  to  be  actinornyces.  The  myce- 
lium had  penetrated  into  the  tubular  glands  and  showed  calcified 
club-shaped  conidia.  The  calcification  of  the  club-shaped  extremi- 
ties had  undoubtedly  prevented  deeper  penetration  of  the  fungus. 
No  other  organs  presented  evidences  of  actinomycosis.  Hochen- 
egg  ("  Fall  von  Actinomykose,"  Wiener  med.  Wochenschrift,  No. 
44,  1886)  presented  a  case  of  actinomycosis  to  the  Medical  Society 
in  the  person  of  a  man  forty-three  years  of  age,  who  had  sustained 
an  injury  of  the  abdomen  nine  mouths  previously,  and  had  since 
that  time  noticed  a  painful  swelling  at  the  seat  of  injury.  In  the 
region  of  the  umbilicus  a  fistulous  opening  formed  which  continued 
to  discharge  a  thin  secretion  in  which  actinomyces  were  constantly 
found.  The  patient  was  very  much  emaciated  and  many  of  the 
teeth  carious.  There  was  no  swelling  about  the  jaws  or  neck. 
Examination  of  organs  of  chest  and  the  sputum  contributed  no 
additional  information.  The  author  expressed  the  opinion  that 
the  inflammatory  swelling  caused  by  the  contusion  furnished  the 


SEAT    OF    PRIMARY'  INVASION.  225 

necessary  conditions  for  the  localization  of  actinomyces  from  the 
intestinal  canal. 

Zemann  ("Ueber  die  Aktinomykose  des  Bauchfells  und  der 
Bancheingeweide  beim  Menschen,"  Wiener  med.  Jahresbericht, 
Hefte  3,  4,  1883)  reports  five  cases  of  actinomycosis  of  the  abdo- 
men. In  four  of  them  the  disease  commenced  with  sharp  lanci- 
nating pains  in  the  abdomen,  and  during  their  course  presented  the 
clinical  picture  of  chronic  peritonitis.  Swellings  could  be  found  in 
one  or  more  places  in  the  anterior  abdominal  wall,  and  the  abscesses 
were  either  incised  or  opened  spontaneously ;  in  three  cases  they 
communicated  with  the  intestinal  canal. 

The  first  case  was  a  woman,  thirty  years  of  age,  who  had  a  fistu- 
lous  opening  in  the  anterior  abdominal  wall,  which  communicated 
with  a  swelling  in  the  left  parametrium.  The  patient  stated  that 
this  swelling  appeared  soon  after  her  last  childbed.  A  constant 
discharge  of  yellowish- red  pus  was  maintained,  in  which,  under  the 
microscope,  numerous  actinomyces  could  be  seen.  The  patient  died 
of  exhaustion,  and  at  the  post-mortem  chronic  parametritis  and 
perimetritis  were  found,  with  extensive  pus  cavities  which  commu- 
nicated with  the  rectum  and  bladder.  The  second  case  occurred  in 
a  person  eighteen  years  of  age,  who,  during  life,  had  suffered  from 
a  large  abscess  in  the  abdominal  cavity  under  the  right  lobe  of  the 
liver,  which  communicated  with  the  intestinal  canal  and  had  led  to 
numerous  fistulous  openings  in  the  anterior  abdominal  wall.  At 
the  necropsy  a  loop  of  the  ileum  was  found  perforated  and  in  com- 
munication with  the  abscess  cavity.  The  pus  contained  numerous 
actinomyces.  In  the  third  case  the  diagnosis  was  made  post-mortem 
by  the  discovery  of  actinomyces  in  the  pus.  The  disease  was  located 
in  the  lower  portion  of  the  ileum  and  caecum,  where  it  had  caused 
suppuration  and  numerous  adhesions. 

The  most  remarkable  and  interesting  history  is  connected  with 
the  fourth  case.  A  robust,  well-nourished  woman,  forty  years  of 
age,  was  attacked  quite  suddenly  with  pain  in  the  stomach,  high 
temperature,  diarrhoea,  and  vomiting,  followed  by  cerebral  symp- 
toms and  death.  At  the  necropsy  the  right  Fallopian  tube  was 
found  transformed  into  a  large  abscess,  both  extremities  of  tube 
closed,  walls  of  sac  lined  with  granulations  containing  actiuomyces. 
The  fifth  patient  was  fifty  years  of  age,  and  had  suffered  for  a  long 
time  from  lancinating  pain  in  the  abdomen ;  a  fistulous  opening 
formed  in  the  umbilical  region  and  discharged  a  thin,  yellowish- 
green  pus.  The  post-mortem  showed  actinomycosis  of  the  peri- 
toneum, small  intestine,  left  ovary  and  liver,  large  abscess  among 
intestinal  coils,  perforation  of  small  intestine  and  bladder.  In  the 
upper  part  of  the  small  intestine  small  pigmeuted  cicatrices  were 
found.  In  all  of  the  above  cases  the  microscopical  examination 

15 


226  ACTINOMYCOSIS    HOMINIS. 

revealed  the  presence  of  actinomyces  in  the  granulation  tissue,  as 
well  as  in  the  pus  of  the  abscess  cavities. 

But  three  cases  of  actinomycosis  had  been  reported  from  Switzer- 
land until  Langhaus  (Correspondenzblatt  /.  Sehweizerdrzte,  June, 
1888)  recently  increased  this  number  by  three  more  which  came 
under  his  own  personal  observation.  One  affected  the  rnastoid 
region,  while  in  the  two  others  the  entrance  of  the  fungus  took 
place  through  the  alimentary  canal.  In  one  of  these  latter  cases 
the  process  evidently  started  from  the  appendix  vermiformis,  which 
was  four  centimetres  in  length,  the  end  of  which  appeared  as  if 
transversely  cut  in  an  abscess  cavity  the  size  of  a  walnut.  The 
abscess  was  on  the  right  side  of  the  bladder,  and  so  deep  in  the 
pelvis  that  during  life  it  could  not  be  located.  The  abscess  pur- 
sued a  chronic  course,  and  the  walls  were  well  defined ;  no  sign  of 
chronic  or  acute  peritonitis.  Furthermore,  the  mucous  membrane 
of  the  appendix  was  studded  with  cicatrices,  and  presented  a  slate- 
color.  The  principal  seat  of  the  actiuomycotic  process  was  in  the 
liver.  The  second  case  presented  marked  symptoms  of  perityphlitic 
abscess  during  life. 

The  necropsy  showed  perforation  of  the  caecum  and  ascending 
colon.  No  cicatrices  in  the  mucous  membrane  or  surrounding 
tissues.  In  all  probability  the  perforations  occurred  from  without 
inward. 

Lueniug  and  Hauau  (Correspondenzblatt  f.  Schweizerdrzte,  1889, 
No.  16)  report  a  very  interesting  case  of  primary  actinomycosis  of 
the  colon,  with  metastatic  deposit  in  the  liver.  The  patient  was  a 
man  twenty-eight  years  of  age,  who  in  1880  suffered  from  an  acute 
abdominal  affection  which  at  the  time  was  diagnosticated  as  typhlitis. 
Four  years  later  he  suffered  from  a  second  attack,  which  presented 
the  appearances  of  intestinal  obstruction.  He  was  very  ill  for  eight 
days,  when  the  symptoms  of  obstruction  subsided,  and  he  made 
a  slow  recovery.  During  the  year  1887  he  had  a  third  attack, 
attended  by  high  fever  and  absolute  constipation  for  eight  or  ten 
days.  During  the  month  of  December  of  the  same  year  he  had 
another  but  less  severe  attack,  and  at  this  time  a  hard  swelling 
made  its  appearance  in  the  right  side  of  the  abdomen.  From  this 
time  until  he  was  admitted  into  the  hospital,  April  5, 1888,  he  was 
confined  to  bed.  The  patient  was  at  this  time  greatly  emaciated, 
with  a  temperature  from  38.4°  to  39.8°  C.  Swelling  the  size  of  a 
fist  in  the  right  side  of  the  abdomen  half  way  between  umbilicus 
and  anterior  superior  spine  of  the  ilium.  Externally  this  swelling 
presented  redness  and  oedema.  Fluctuation  indistinct.  Deep  pal- 
pation showed  that  swelling  extended  to  right  hypochoudrium. 
Abdomen  not  tympanitic.  Swelling  painful  and  tender,  pain  ex- 
tending to  spermatic  cord  and  testicle  on  same  side.  A  few  days 


SEAT    OF    PRIMARY    INVASION.  227 

later  abscess  was  incised  and  nearly  a  pint  of  brownish  pus  having 
a  feculent  odor  escaped.  Digital  exploration  revealed  an  irregular 
cavity  the  walls  of  which  at  some  points  were  plainly  lined  with 
intestinal  coils.  Disinfection  and  drainage.  As  the  symptoms  did 
not  improve  materially  the  abscess  cavity  was  again  scraped  out  and 
disinfected  four  weeks  later.  After  this  operation  it  was  noticed 
that  the  pus  contained  yellow  granules,  which  under  the  micro- 
scope were  shown  to  be  actinomyces.  The  abscess  was  incised  a 
third  time,  but  the  patient  showed  no  improvement,  and  died  Octo- 
ber 9th.  The  autopsy  revealed  primary  actinomycosis  of  ascending 
colon  with  multiple  fistulous  perforations,  metastatic  actinomycosis 
of  liver  with  perforation  of  one  of  the  foci  into  the  hepatic  vein, 
and  multiple  metastases  in  lungs. 

These  observations  warrant  the  opinion  that  the  mucous  mem- 
brane of  the  intestinal  canal  is  a  frequent  seat  of  primary  localiza- 
tion of  the  actinomyces,  thus  corroborating  the  statements  made  by 
Johne  in  reference  to  this  disease  in  animals. 

3.  Inhalation  actinomycosis.  The  case  of  actiuomycotic  abscess 
of  the  lung  caused  by  the  inhalation  of  an  infected  tooth,  reported 
by  Israel,  has  already  been  cited  as  an  illustration  in  showing  that 
decayed  teeth  frequently  serve  the  purpose  of  an  infection-atrium 
in  actinomycosis  of  the  mouth.  Cases  of  primary  actinomycosis  of 
the  lungs,  however,  have  been  observed  in  which  no  such  carrier  of 
the  contagium  could  be  found,  and  in  which  infection  must  have 
occurred  by  the  direct  inhalation  of  the  fungus  or  its  spores. 

Szenasy  ("  Ein  Fall  von  Lungen-Aktinornykose,"  Centralblatt  f. 
Chirurgie,  1886,  !N"o.  41)  found,  in  the  case  of  the  wife  of  a  butcher, 
who  had  suffered  for  nine  years  from  severe  pain  in  the  right  side 
of  the  chest,  latterly  attended  by  a  severe  cough  in  the  right  mam- 
mary region,  a  fluctuating  swelling  the  size  of  a  hen's  egg  covered 
with  normal  skin.  On  the  outer  side  of  this  swelling,  in  the  inter- 
costal space  between  the  third  and  fourth  ribs,  another  swelling 
existed  double  in  size  and  elongated  in  shape  and  with  indistinct 
margins.  This  latter  swelling  had  been  noticed  for  nine  years,  and 
was  tender  to  the  touch.  Auscultation  over  the  fourth  and  fifth 
intercostal  spaces  on  the  healthy  side  revealed  bronchial  breathing 
and  diffuse  bronchial  rabies.  Temperature  38.4°  C.  (101.1°  F.). 
Urine  contained  a  trace  of  albumin.  By  aspiration  one  hundred 
and  fifty  cubic  centimetres  of  thick  yellow  pus  were  removed,  which 
contained  colonies  of  actinomyces.  Actinomyces  were  also  found  in 
the  sputum.  The  patient  had  carious  teeth,  but  no  signs  of  actino- 
mycosis could  be  detected  in  the  mouth. 

Canali  (quoted  by  Partsch)  communicates  the  clinical  history  of 
a  girl,  fifteen  years  of  age,  who  had  suffered  for  eight  years  from  a 
cough,  attended  by  a  scanty  fetid  expectoration.  Inspection  and 


228  ACTINOMYCOSIS     HOMIXIS. 

percussion  yielded  only  negative  results.  Auscultatory  symptoms 
pointed  to  a  diffuse  catarrh.  Under  the  microscope  the  sputum  was 
seen  to  contain  pus  corpuscles,  epithelial  cells,  and  numerous  actino- 
myces.  No  primary  source  of  infection  could  be  found  in  the 
mouth,  pharynx,  or  nose.  Other  cases  of  primary  actinomycosis  of 
the  lung  have  recently  been  reported  by  Laker  ("  Beitrag  zur  Char- 
akteristik  der  primaren  Lungen-Aktinomykose,"  Wiener  med.  Presse, 
1889).  Lindt  ("Ein  Fall  von  primarer  Lungenspitzen-Aktinomy- 
kose,"  Schweiz.  Correspondenzblatt,  Nos.  9-12, 1889),  and  Butimeyer 
("  Ein  Fall  von  primarer  Lungen-Aktinomykose,"  Berl.  klin. 
Wochenschrift,  No.  3,  1889).  In  all  of  these  cases  the  disease 
proved  fatal  by  the  extension  of  the  actinomycotic  process,  followed 
by  the  formation  of  large  abscesses.  In  Lindt's  case  the  disease  ex- 
tended from  the  lungs  to  the  muscles  of  the  neck.  Moosbriigger 
interprets  the  mechanism  of  the  ingress  of  actinomyces  by  assuming 
that  the  fungus  enters  the  bronchial  tubes  during  inspiration,  and 
becomes  at  first  deposited  upon  the  mucous  membrane,  in  which  its 
presence  and  growth  cause  a  destruction  of  the  epithelial  cells,  when 
it  reaches  the  submucous  and  peribronchial  tissues,  in  which  a  nodule 
of  granulation  tissue  is  produced,  which  by  pressure  induces  degen- 
erative changes  and  gradual  destruction  of  the  bronchial  wall  for 
further  infection.  He  believes  that  the  peribrouchial  lymphatic 
vessels  and  glands  take  an  active  part  in 'the  local  diffusion  of  the 
process,  as  they  furnish  an  avenue  for  the  distribution  of  the  germ 
or  its  spores.  He  claims  the  existence  of  an  actinomycotic  lymph- 
angitis, but  confesses  that  he  has  never  seen  the  fungus  inside  of 
lymphatic  vessels.  As  soon  as  the  fungus  reaches  the  pulmonary 
tissues  it  gives  rise  to  parenchymatous  inflammation,  the  first  pro- 
duct of  which  is  always  granulation  tissue,  which,  at  a  later  stage 
and  under  the  influence  of  a  secondary  infection  with  pus-microbes, 
undergoes  transformation  into  pus  corpuscles  and  the  formation  of 
abscesses. 

ACTINOMYCOSIS  OF  BRAIN. — Bollinger  has  placed  on  record 
the  first  case  of  primary  actinomycosis  of  the  brain  ( "  Ueber 
primare  Aktinomykose  des  Gehirus  beim  Menschen,"  Munch- 
ener  med.  Wochenschrift,  1887,  No.  41.  The  patient  was  twenty- 
six  years  of  age.  The  intra  vitam  diagnosis  was  tumor  of  the 
brain ;  the  most  prominent  symptoms  were  severe  headache, 
paralysis  of  the  left  abducens,  congestion  of  optic  papilla,  and 
momentary  unconsciousness.  The  swelling  in  the  brain,  found  on 
autopsy,  presented  the  characteristic  features  of  a  cysto-myxoma  in 
the  third  ventricle ;  all  of  the  ventricles  were  found  considerably 
dilated.  The  swelling  contained  numerous  colonies  of  actinomyces 
in  all  possible  stages  of  development.  The  tendency  to  suppuration 
of  the  tissues  usually  found  in  all  cases  of  actinomycosis  in  man  was 


ACTING  MYCOSIS    OF    BEAIX.  229 

entirely  absent  in  this  case.  This  case,  if  any,  appears  to  be  one  of 
crypto-genetic  infection,  as  the  fungus  or  spores  must  have  entered 
somewhere  through  the  cutaneous  or  mucous  surface  without  pro- 
ducing the  disease  at  the  portio  invasionis,  and,  localizing  in  the 
brain  by  embolism,  produced  primary  actinomycosis  in  this  organ. 
Keller  (British  Medical  Journal,  March  2  ),  1890)  reports  a  case 
of  actinomycosis  of  the  brain  secondary  to  same  disease  in  chest- 
wall  in  which  a  correct  diagnosis  was  made  during  life,  and  an 
operation  performed  followed  by  temporary  improvement.  The 
patient  was  a  woman,  forty  years  of  age,  who  suffered  from  pleurisy 
followed  in  six  months  by  an  abscess  over  the  cartilage  of  sixth 
rib  and  also  the  eleventh.  Both  were  incised,  contents  removed 
by  sharp  spoon,  and  drained.  They  did  not  communicate  with  the 
pleural  cavity,  nor  were  the  ribs  affected.  These  abscesses  healed, 
leaving  one  small  fistula.  Two  years  later  she  complained  of 
increasing  paresis  of  left  arm.  Diagnosis  of  actinomycosis  in  the 
motor  area  was  made,  but  patient  declined  operation.  Convulsions 
of  the  left  arm  soon  set  in  several  times  taking  the  course  of  corti- 
cal epilepsy.  The  paresis  extended  to  left  lower  extremity  and  left 
side  of  the  face.  Headache,  vomiting,  and  complete  loss  of  con- 
sciousness followed,  which  developed  into  deep  coma,  and  when 
apparently  moribund  operation  was  consented  to.  Dr.  Burger, 
without  any  anaesthetic,  trephined  the  skull  over  the  middle  of  the 
right  ascending  parietal  convolution,  incised  the  dura  mater  and 
discolored  brain  substance  and  removed  two  ounces  of  thin  greenish 
pus  which  contained  great  quantities  of  actinomyces.  Soon  after 
opening  the  abscess  she  recovered  from  the  deep  coma,  and  called 
for  water.  On  the  following  day  consciousness  returned.  On  the 
eighth  day  facial  paralysis  disappeared  and  she  could  move  the  leg. 
Six  months  after  the  operation  she  began  to  walk  around.  During 
the  next  few  months,  the  paralytic  lesions  materially  improved, 
but  there  still  remained  paresis  of  left  arm  and  slight  contraction 
of  the  fingers.  In  two  months  the  wound  had  healed,  and  the 
patient  felt  very  well.  Several  (eleven)  months  later,  grave  symp- 
toms of  increasing  paralysis,  headache,  and  convulsions  returned. 
Dr.  Burger  reopened  the  brain  and  removed  a  considerable  quantity 
of  pus.  This  was  followed  by  no  material  improvement,  and  the 
patient  died  a  few  days  afterwards.  At  the  post-mortem  the 
middle  third  of  the  right  frontal  and  parietal  convolutions  was 
occupied  by  a  large  mass  of  newly-formed  tissue  protruding  over 
the  surface  of  the  brain,  reaching  down  into  the  substance  of  the 
brain  for  one  inch.  Underneath  it,  deeply  buried  in  the  white 
substance,  an  unopened  encapsulated  abscess  the  size  of  a  nutmeg 
was  discovered. 


CHAPTEK   XXI. 

GONORRHOEA. 

HISTORY. — In  no  other  disease  has  the  suspicion  of  a  specific 
infective  cause  been  so  general  and  entertained  for  such  a  long 
time  as  in  gonorrhoea.  Hallier,  Donne,  Jonissou,  Salisbury,  and 
many  others,  made  diligent  search  for  its  contagium,  which,  by 
them,  was  believed  to  be  a  living  organism.  Following  Koch's 
improved  method  of  investigation,  Neisser  finally  discovered  the 
specific  microbe  in  gonorrhoeal  pus  in  the  year  1879  (Centralblatt 
f.  d.  med.  Wissensch.,  1879,  No.  28).  He  called  the  new  microbe 
gonococcus.  He  described  the  microorganism  as  a  diplococcus 
which  differed  from  the  other  varieties  of  this  species  of  parasites 
in  being  always  found  in  clumps  of  from  ten  to  twenty,  surrounded 
by  a  mucous  envelope.  Neisser's  communication  was  soon  followed 
by  a  number  of  exhaustive  publications,  and  to-day  the  literature 
on  the  gouococcus  has  become  quite  extensive. 

DESCRIPTION  OF  THE  GONOCOCCUS. — The  gonococcus  always 
occurs  in  pairs,  and  is,  therefore,  a  diplococcus.  The  cocci  appear 
as  hemispherical  bodies  with  their  flattened  surfaces  in  apposition, 
which  imparts  to  the  microbe  the  characteristic  biscuit-shaped 
appearance.  The  gouococci  are  found  in  clusters  or  clumps  upon, 
or,  what  is  more  probable,  as  Bumm  asserts,  within  the  pus  cor- 
puscles of  gonorrhoeal  pus.  Their  intracellular  location  was 
shown  by  Bumm  by  examining  pus  corpuscles  in  water :  when, 
after  imbibition  of  water,  the  cells  became  swollen,  the  cocci  could 
be  seen  between  the  molecular  granules  of  the  protoplasm.  The 
microbes  within  the  corpuscle  may  become  so  numerous  as  to  fill 
the  entire  space,  with  the  exception  of  the  nucleus.  Bockhardt 
and  Haab  asserted  that  they  found  them,  also,  inside  of  the  nucleus, 
but  this  has  not  been  confirmed  by  some  of  the  ablest  and  most 
careful  bacteriologists. 

Legrain  ("  Eecherches  stir  les  Kapports  qu'affecte  le  Gonococcus 
avec  les  Elements  du  Pus  blenorrhagique,"  Arch,  de  Physiol.  norm, 
et  pathol,  1887,  No.  6)  on  studying  the  behavior  of  the  cellular 
elements  of  gonorrhoeal  pus  and  the  gonococci,  has  found  that  in 
the  very  incipiency  of  the  disease  the  secretion  contains  an  abund- 
ance of  epithelia  and  few  pus  corpuscles;  the  gonococci  are  abund- 
ant on  the  surface  of  the  epithelia  and  few  in  the  interior  of  the 


PLATE    XII. 


m 

9 


c 

(&&  dii  it 


Gonococcus.     (After  Bumm.) 
«.  From  a  pure  culture. 

b.  From  a  blennorrhoeic  conjunctival  secretion  ;  an  epithelial  cell 
covered  with  cocci ;  a  pus  cell  with  cocci  in  the  protoplasm  ;  a  pus  cell 
completely  filled  with  cocci ;  a  free  mass  of  cocci  in  close  proximity 
to  a  pus  cell  (Seibert).     Oc.  2. 

c.  Scheme  of  development  of  gonococci. 


STAINING.  231 

pus  corpuscles.  At  this  stage  inflammation  affects  only  the  most 
superficial  portion  of  the  mucous  membrane.  In  a  short  time, 
however,  the  gonococcus  penetrates  into  the  lymph  spaces  and  the 
inflammation  extends  more  deeply.  From  the  second  to  the 
third  day,  as  the  secretion  becomes  more  profuse,  the  epithelial 
cells  are  less  numerous  and  the  pus  corpuscles  are  in  proportion 
more  abundant,  and  from  two  to  three  of  them  to  every  hundred 
contain  gonococci,  usually  two  to  three  congregated  closely  together 
in  one  corpuscle.  During  the  progress  of  the  acute  stage  the  epi- 
thelial cells  become  more  and  more  scanty,  while  the  pus  corpus- 
cles containing  cocci  increase  in  number  so  that  finally  one  in  every 
five  contains  the  specific  microbes. 

During  the  subacute  stage,  about  the  fourth  week,  the  epithelial 
cells  again  have  become  more  numerous,  about  in  the  proportion  of 
one  to  every  eight  or  ten  pus  corpuscles.  But  few  of  the  cells 
contain  gonococci,  while  the  pus  corpuscles  are  freely  charged  with 
them.  In  chronic  cases  of  gonorrhoea  the  epithelial  cells  again  are 
more  numerous,  and  most  of  them  contain  gonococci  while  the 
pus  corpuscles  almost  disappear.  Extra-cellular  gonococci  are  also 
numerous.  He  believes  that  gonococci  can  enter  the  nucleus. 

The  size  of  the  gonococcus  varies  according  to  its  age,  and 
depends,  also,  upon  the  nature  of  the  nutrient  medium.  In  the 
mucous  membrane  in  man  they  attain  the  largest  size,  and  measure 
1.6  micromillimetre  from  pole  to  pole,  while  the  width  of  each 
separate  coccus  is  0.8  and  0.6  micromillimetre. 

According  to  Welander  ("  Ueber  den  Eiufluss  der  Keuutniss  der 
Gonococcen  auf  die  Behandlung  der  Gonorrhoeeu,"  Hygiea,  Bd. 
Ixvii.,  1885),  the  gonococcus  multiplies  by  division.  The  first 
change  that  is  observed  is  that  the  coccus  assumes  an  oblong  shape, 
in  the  centre  of  which  a  constriction  takes  place,  which  becomes 
deeper  and  deeper  until  the  segmentation  is  completed.  This  pro- 
cess he  has  only  observed  in  cocci  free  in  the  secretion,  only  excep- 
tionally within  epithelial  cells,  and  never  in  cocci  in  the  interior  of 
pus  corpuscles  or  their  nuclei.  He  was  unable  to  satisfy  himself 
of  the  correctness  of  Bockhardt's  observation  that  the  gonococcus 
multiplies  in  the  interior  of  white  blood-corpuscles. 

STAINING. — The  gonococcus  stains  readily  with  basic  aniline 
dyes,  but  by  using  gentiana,  dahlia,  and  methyl-violet,  the  staining 
becomes  so  intense  that  the  fissure  between  the  cocci  becomes 
obscured,  while  this  is  not  the  case  by  using  concentrated  fuchsin 
solution.  Bumm  claims  that  the  staining  can  be  done  most  success- 
fully with  aniline-violet,  and  that  the  staining  is  less  intense  by 
using  fuchsin. 

Smirnoff  stained  the  gonococci  for  microscopical  examination  as 
follows :  The  slide  is  covered  with  a  thin  layer  of  pus,  dried,  and 


232  GONORRHCEA. 

immersed  for  a  minute  in  a  solution  of  methyl-blue,  composed  of  1 
part  of  methyl-blue,  33  parts  of  alcohol,  and  66  parts  of  water, 
after  which  it  is  washed  in  water,  and  after  drying  mounted  in 
Canada  balsam. 

Schuetz  (Munch,  med.  Wochensehrift,  No.  14. 1889)  recommends 
the  following  method  :  The  carefully  prepared  cover-glass  prepara- 
tions are  immersed  for  from  five  to  ten  minutes  in  a  cold,  filtered, 
and  saturated  solution  of  methylene-blue  in  five  per  cent,  carbolic 
acid  water.  They  are  then  washed  in  distilled  water,  and  after- 
ward placed  for  a  moment  in  a  solution  of  five  drops  of  acetic  acid 
in  twenty  cubic  cm.  of  distilled  water,  and  again  washed  in  pure 
water.  Everything  in  the  specimen  is  now  decolorized,  except 
the  gonococci,  which  remain  distinctly  blue.  Double  staining 
with  safranin  can  now  be  done  when  the  gonococci  and  epithelial 
cells  show  a  blue  color,  while  the  pus  cells  and  their  nuclei  are 
found  salmon-colored. 

CULTIVATION. — The  cultivation  of  the  gonococcus.  is  associated 
with  many  difficulties.  Bumm  (Der  Microorganismus  der  Gonor- 
rhceischen  Schleimhaut-Erkmnkung,  Gronococcus  Neisser,  Wiesbaden, 
1887),  succeeded  best  in  obtaining  a  pure  culture  upon  blood  serum 
of  the  calf  and  sheep,  especially  if  to  the  coagulated  serum  a  little 
serum  from  human  blood  is  added,  and  after  coagulating  again  the 
nutrient  medium  is  kept  at  an  even  temperature  of  30°  to  34°  C. 
(86°  to  93.2°  F.).  If  the  temperature  exceeds  38°  C.  (100.4°  F.), 
the  gonococci  are  invariably  destroyed.  By  using  the  above  nutrient 
substance  Bumm  observed,  eighteen  to  twenty-four  hours  after  in- 
oculation, the  whole  surface  covered  with  the  growth.  The  culture 
grows  only  upon  the  surface  and  does  not  liquefy  the  soil.  The 
addition  of  very  mild  antiseptics  to  the  soil  completely  prevented 
the  growth  of  the  microbe.  Cultivations  on  agar-agar  and  gelatin 
never  proved  successful. 

Kreis  ("  Beitrage  zur  Kenntniss  der  Gonococcen,"  Wiener  med. 
Woehenschrifi,  1885,  Nos.  30-32)  succeeded  in  cultivating  the  gono- 
coccus upon  agar-agar  with  an  admixture  of  Kemmerich's  meat- 
peptone,  kept  at  a  temperature  of  30°  to  40°  C.  (86°  to  104°  F.). 
The  culture  soil  was  not  liquefied  and  the  size  of  the  cocci  was  uni- 
form; addition  to  the  soil  of  2  per  cent,  alkali  arrested  further 
growth  of  the  culture. 

Krause  ("Die  Micrococcen  der  Blenorrhcea  neonat.,"  Centralblatt 
/.  d.  prakt.  Augenheilk.,  1882,  p.  134)  made  cultivation  experiments 
upon  meat-iufusion-peptone-gelatin,  but  failed  in  many  instances. 
After  many  trials  with  serum  of  animal  blood  he  finally  succeeded 
in  obtaining  a  culture  by  placing  the  glass  tubes  in  an  incubator, 
in  which  the  temperature  was  kept  from  30°  to  38°  C.  (86°  to 
100.4°  F.).  The  culture  appeared  on  the  surface,  starting  from 


INOCULATION    EXPERIMENTS.  233 

the  puncture  as  a  yellowish-gray  film  which   grew  very  slowly. 
Leistikow  and  Loffler  also  succeeded  best  with  blood  serum. 

INOCULATION  EXPERIMENTS. — 1.  In  man.  Bumrn  found  two 
females  who  were  willing  to  submit  to  inoculation  experiments. 
In  one  a  pure  culture  obtained  upon  human  blood-serum,  and  in 
the  other  a  pure  culture  grown  upon  animal  blood-serum,  were 
applied  to  the  urethra.  In  both  cases  a  typical  gonorrhoea  was  de- 
veloped. Numerous  gonococci  could  be  found  in  the  pus.  These 
experiments  aiforded  him  a  reliable  proof  of  the  etiological  signifi- 
cance of  the  gonococcus. 

Bokai  (Allg.  med.  Central  Zeitung,  1880,  No.  74)  produced  gon- 
orrhoea in  two  men  by  the  injection  of  a  pure  culture  into  the 
urethra. 

Bockhardt  injected  into  the  urethra  of  a  man,  forty -five  years  of 
age,  suffering  from  a  fatal  disease,  a  pure  culture  of  the  gonococcus 
grown  upon  meat-infusion-peptone-gelatin,  and  produced  a  typical 
gonorrhoea.  On  the  third  day  the  secretions  were  examined  for  the 
specific  microbes,  which  were  found  in  abundance.  On  the  tenth 
day  the  patient  died  of  hypostatic  pneumonia.  The  post-mortem 
revealed  the  existence  of  gonorrhoea!  cystitis  and  nephritis.  In  the 
pus  of  these  organs,  and  in  the  sections  from  the  fossa  navicularis, 
numerous  gonococci  were  found  in  the  nuclei  of  the  white  blood- 
corpuscles,  while  the  connective-tissue  spaces  and  lymphatic  channels 
appeared  to  be  almost  completely  blocked  by  them.  The  compli- 
cations which  were  found,  he  regards  as  the  direct  result  of  the 
diffusion  of  the  specific  microbes. 

Welander  ("  Einige  Versuche  zur  Feststellung  der  Vitaltitat 
der  Gonokokken  ausserhalb  des  menschlichen  Korpers,"  Schmidt's 
Jahrbucher,  B.  ccxiv.  p.  39)  studied  the  resisting  power  of  the  gono- 
coccus outside  of  the  organism  by  inoculation  experiments.  As 
early  as  1884  he  made  inoculations  with  negative  results  with  dried 
gonorrhoeal  pus  removed  three  hours  to  eight  days  before  directly 
from  the  urethra.  During  the  year  1886  the  same  experiments 
were  repeated.  In  all  cases  in  which  inspissated  pus  was  used  the 
inoculation  proved  harmless.  The  result  was  the  same  whether  the 
pus  was  used  in  the  dry  form,  or  moistened  with  water.  These 
experiments  prove  that  the  gonococci  lose  their  virulence  during 
the  process  of  drying.  To  ascertain  how  long  the  gonococci  will 
retain  their  virulence  in  fluid  pus,  he  removed  the  pus  directly 
from  the  diseased  urethra  and  preserved  it  in  capillary  glass  tubes 
in  the  same  manner  as  vaccine  virus  is  preserved.  Eour  experi- 
ments were  made.  In  three,  the  inoculations  were  made  from  one 
to  several  days  after  removal ;  in  all  the  results  were  negative.  In 
the  fourth  case,  the  inoculation  was  made  with  pus  removed  three 
hours  before.  On  the  third  day  the  infected  patient  complained  of 


234:  GOXOEKHCEA. 

a  burning,  smarting  sensation  in  the  fossa  uavicularis,  which  was 
followed  by  a  typical  gonorrhoea  two  days  later.  In  the  last  case 
the  pus  was  kept  at  the  temperature  of  the  body,  which  was  not 
done  in  the  other  experiments.  Two  experiments  he  made  with 
pus  exposed  to  a  temperature  near  the  freezing-point,  with  negative 
results  in  both  instances. 

2.  In  animals.  No  uniform  results  have  been  obtained  by  inocu- 
lation experiments  in  animals,  not  because  the  gonococci  are  not  the 
cause  of  gonorrhoea,  but  on  account  of  the  immunity  of  most  animals 
to  this  form  of  infection.  Lundstrom  claims  that  he  obtained  a 
pure  culture  upon  Koch's  gelatin,  and  that  inoculations  with  this 
produced  typical  gonorrhoea  in  dogs;  in  the  purulent  secretion 
numerous  gonococci  could  be  found. 

Bumm  states  that  pure  gonorrhoeal  pus  can  be  injected  into  the 
subcutaneous  cellular  tissue  of  animals  without  causing  reaction, 
and  that  if,  after  twenty-four  hours,  an  incision  is  made,  and  some 
of  the  pus  which  was.  injected  is  removed,  it  will  be  found  that  the 
cells  are  still  in  good  condition,  but  that  the  cocci  have  disappeared. 

That  the  gonococcus  has  a  special  predilection  for  the  mucous 
membranes  is  well  shown  by  the  regularity  with  which  purulent 
ophthalmia  is  produced  by  the  infection  of  the  conjunctiva  with 
gonorrhoeal  pus. 

The  ease  and  regularity  with  which  gonorrhoea  can  be  produced 
in  man  by  inoculation  with  a  pure  culture  of  the  gouococcus,  fur- 
nishes the  punctum  saliens  which  characterizes  this  microbe  as  the 
materia  peccans  of  gonnorrhoea. 

ACTION  OF  GONOCOCCUS  ON  THE  TISSUES. — The  presence  of  the 
gouococcus  so  far  has  been  demonstrated  in  the  urethra,  bladder, 
kidney  (Bockhardt),  in  perimetritic  abscesses  following  gonorrhoea, 
in  the  purulent  contents  of  joints  in  gonorrhoeal  synovitis,  the  con- 
junctiva, rectum  (Bumm),  in  the  uterus,  cervix,  vagina,  vulva,  and 
in  Bartholin's  glands.  The  real  seats  of  gonorrhoeal  infection  are 
mucous  membranes  lined  by  columnar  epithelium,  or  epithelium 
which  closely  resembles  it.  The  grouping  of  the  microbe  in  the 
pus  corpuscles,  from  a  diagnostic  point  of  view,  is  more  important 
than  its  diplococcus  form.  For  the  purpose  of  studying  the  eifects 
of  this  microbe  on  the  tissues,  Bumm  examined  twenty-six  specimens 
of  gonorrhoeal  conjunctivitis.  When  the  gonococcus  is  brought  in 
contact  with  the  conjunctiva  or  the  urethra,  the  first  growth  takes 
place  upon  the  surface  of  the  epithelial  layer,  as  its  entrance  into 
the  deeper  layers  meets  with  difficulty,  and  Bumm  asserts  that  it 
penetrates  deeper  only  after  the  epithelial  layer  has  become  some- 
what loosened  by  inflammatory  changes — that  is,  after  intercellular 
passages  have  formed.  A  dense,  compact  layer  of  epithelial  cells 
furnishes  a  safe  protection  against  gouorrhceal  infection,  so  much 


ACTION    OF    GOXOCOCCUS    ON    THE    TISSUES.          235 

so,  that  Bumm  claims  that  a  true  gonorrhoea  in  the  vagina  of  adults 
is  impossible,  while  it  does  occur  in  children.  The  gonococcus 
reaches  the  deeper  tissue  layers  exclusively  by  its  growth  into  the 
intercellular  passages,  consequently  the  advance  is  very  slow.  The 
first  effect  of  the  infection  upon  the  mucous  membrane  is  an  increase 
of  the  physiological  secretion — a  thin  mucous  fluid.  Suppuration 
is  not  the  result  of  the  cocci,  but  of  chemical  substances  which  are 
produced  by  them,  as  pus  corpuscles  appear  before  the  microbes 
have  reached  the  vascular  layer  of  the  mucous  membrane.  As  the 
pus  corpuscles  enter  the  epithelial  layer  the  latter  becomes  still  looser 
and  some  of  the  cells  exfoliate.  After  this  stage  the  pus  cells  are 
the  structures  in  which  the  gonococci  are  developed.  Cessation  of 
the  suppurative  process  is  not  always  a  sign  that  infection  has  also 
ceased,  as  during  the  latent  stage  only  a  catarrhal  secretion  is  pres- 
ent, but  suppuration  may  be  lighted  up  again  at  any  time  under  the 
influence  of  additional  causes  which  produce  an  aggravation  of  the 
chronic  inflammatory  process. 

In  serous  cavities  gonorrhoeal  pus  produces,  as  a  rule,  a  circum- 
scribed abscess.  Sinclair,  in  his  excellent  monograph  (Gronorrhceal 
Infection  in  Women,  London,  1888,  p.  79),  after  describing  the  gonor- 
rhoeal infection  from  the  vagina,  says :  *'  The  proper  character  and 
results  of  the  pathogenous  activity  of  the  gonorrhoeic  microbes  are 
therefore  seen,  pure  and  unadulterated,  in  the  tubes.  They  cause 
purulent  inflammation  of  the  mucous  membrane,  but  the  sur- 
rounding connective  tissue  remains  free  from  them.  The  gouor- 
rhoeic  tubal  pus  is  evacuated  into  the  peritoneum,  and  whereas  in 
other  conditions  the  bursting  of  an  abscess  into  the  abdominal 
cavity  is  followed  by  the  gravest  consequences,  in  this  case  the 
whole  process  terminates  with  a  circumscribed  inflammation,  encap- 
sulating the  exuded  pus.  The  cause  of  this  difference  is  the  varying 
pathogenic  value  of  the  organisms  which  are  contained  in  the  pus. 
A  puerperal  pelvic  cellulitic  abscess  bursting  into  the  peritoneum 
causes  general  peritonitis,  because  it  contains  pyogenous  strepto- 
cocci, which  rapidly  multiply  in  serous  cavities  and  are  capable  of 
exerting  the  most  deleterious  effects.  Gonorrhoeal  tubal  pus  cannot 
do  this;  its  microbes  do  not  find  in  the  peritoneum  conditions  for 
their  increase ;  the  pus,  therefore,  acts  as  an  aseptic  foreign  body, 
becomes  encapsulated,  and  is  finally  absorbed. " 

That  this  favorable  termination  does  not  always  follow  gonor- 
rhoeal infection  of  the  peritoneal  cavity  is  well  shown  by  a  case 
reported  by  Loven  ("  Fall  von  Gonorrhea  bei  einem  fiinf  jahrigen 
Madchen ;  Peritonitis ;  Tod/7  Schmidt's  Jahrbiicher,  B.  ccxiv.  p. 
39)  which  is  by  no  means  an  isolated  one.  The  source  of  infection 
could  not  be  learned  in  this  case,  but  the  diagnosis  of  gonorrhceic 
ascending  infection  was  positive.  The  disease  commenced  as  an 


236  GONOKRHCEA. 

ordinary  vulvo-vaginal  blenuorrhoea,  which  consecutively  extended 
to  the  uterus  and  Fallopian  tubes,  and  terminated  in  pelvic  and 
diffuse  peritonitis.  It  is  possible  that  in  this  case  a  secondary 
infection  had  taken  place,  as  at  the  necropsy  chain  cocci  were  found 
in  the  peritoneal  cavity. 

THE  GONOCOCCUS  AND  PURULENT  OPHTHALMIA. — Haab  (Der 
MicroGoscus  der  Btenorrhoea  neonat.,  Wiesbaden,  1881)  showed  that 
the  microorganism  found  in  gonorrhoeal  pus  and  the  secretion 
of  purulent  ophthalmia  are  identical.  He  placed  great  stress  on 
the  fact  that  according  to  his  own  observations  the  gonococcus  is 
always  present  in  the  secretions  of  purulent  ophthalmia,  and  that 
it  is  never  found  in  the  simple  inflammatory  or  catarrhal  form. 

Widmark  (u  Bakteriologische  Studien  iiber  purulente  Conjuncti- 
vitis und  gonorrhceische  Urethritis/'  Hygoei,  B.  xlvi.,  1884)  exam- 
ined twenty-four  cases  of  purulent  conjunctivitis  in  reference  to  the 
existence  of  the  gonococcus,  using  "Welander's  method.  In  most  of 
the  cases  he  found  the  microbe.  The  gonococcus  was  found  free  in 
the  secretions,  the  pus  corpuscles,  and  the  epithelial  cells.  He  be- 
lieves, with  Welauder,  that  during  the  period  of  incubation  the 
microbes  remain  attached  to  the  epithelial  cells,  and  are  reproduced 
there,  whence  they  later  penetrate  into  the  deeper  tissues.  After  a 
time  they  almost  disappear  in  the  secretions,  without,  at  the  same 
time,  any  improvement  taking  place  in  the  catarrhal  condition. 
From  a  practical  standpoint  these  observations  are  important,  as 
they  prove  the  importance  of  early  treatment  before  the  microbes 
have  passed  beyond  the  reach  of  local  applications  of  autimycotic 
remedies. 

Among  other  prominent  ophthalmologists,  Sattler,  Lebert,  and 
Hirschberg  recognize  the  gonococcus  of  Neisser  as  the  specific  cause 
of  gonorrhoea  and  its  identity  with  the  coccus  found  in  specific 
purulent  ophthalmia. 

THE  GONOCOCCUS  IN  ABSCESSES. — Opinions  are  divided  in 
reference  to  the  pyogenic  properties  of  the  gonococcus.  In  infec- 
tions of  the  mucous  membrane  its  pus-producing  property  is  well 
known,  but  at  present  is  not  attributed  to  its  direct  effect  on  the 
tissues,  but  to  the  action  of  ptomaines  which  it  produces.  A  num- 
ber of  cases  have  been  reported  which  appear  to  show  that  under 
certain  circumstances  the  microbe  enters  the  circulation  and  is  the 
cause  of  metastatic  abscesses,  and  on  this  account  should  be  classed 
with  the  pus-microbes. 

Horteloup  relates  the  case  of  a  man,  twenty-seven  years  of  age, 
who  had  suffered  from  gonorrhoea  for  several  mouths,  in  whom  an 
abscess  formed  in  the  clavicular  region,  which  was  incised,  and  in 
the  pus  numerous  gonococci  were  found. 

Schwarz  (Sammlung  klin.  Vortrage,  1886,  No.  279)  asserts  that 


THE    GOXOCOCCUS    IX    ABSCESSES.  237 

the  gonococcus  is  constantly  found  in  the  effusion  of  joints  in  gon- 
orrhoeal  rheumatism,  in  abscesses  caused  by  gonorrhoea,  and  in  the 
glands  of  Bartholin.  He  further  states  that  it  is  found  free  in  the 
fluid,  but  mostly  it  is  incorporated  in  the  protoplasm  of  pus-corpus- 
cles. Petrone  detected  the  specific  microbe  in  the  effusion  of  joints, 
and  in  the  blood,  in  two  patients  suffering  from  gonorrhoeal  rheu- 
matism. He  regarded  the  joint  complications  as  metastatic  pro- 
cesses caused  by  the  gonorrhoeal  infection. 

Kammerer  ("  Ueber  gouorrhoeische  Gelenkentziindung,"  Central- 
blatt  f.  Chirurgie,  1884,  No.  4)  examined  the  fluid  from  two  cases 
of  gonorrhoeal  arthritis,  and  found  micrococci  present  in  one  and 
absent  in  the  other. 

At  a  meeting  of  the  Gesells.  d.  Aerzte,  in  Zurich,  Prof.  Haab 
(Correspondence,  British  Medical  Journal,  June  2,  1888)  read  a 
paper  on  a  generalized  or  constitutional  gonorrhoeal  infection  devel- 
oping consecutively  to  specific  urethritis.  He  often  met  cases  of 
gonorrhoeal  iritis  and  irido-cyclitis,  as  well  as  of  conjunctivitis, 
originating  without  any  direct  transmission  of  the  urethral  dis- 
charge. In  cases  of  the  latter  kind  no  gonococci  were  present  in 
the  coujunctival  secretion,  the  disease  usually  running  a  mild  and 
favorable  course.  He  further  cites  a  striking  case  of  general  infec- 
tion after  urethral  gonorrhoea,  in  which  death  was  threatening  in 
consequence  of  extreme  exhaustion,  caused  by  a  continuous,  uncon- 
trollable fever  of  many  weeks7  duration.  The  man  was  suffering 
from  effusion  into  his  knee-  and  elbow-joints,  abscesses  in  the  left 
axilla,  prolonged  and  obstinate  cystitis,  and  double  ophthalmia  of 
the  severest  kind,  ending  in  complete  destruction  of  one  eye  and  a 
serious  disorganization  of  the  other.  No  microbes  were  found  in 
the  articular  exudation,  but  the  axillary  abscess  was  found  to  con- 
tain staphylococcus.  Prof.  Haab  seems  to  think  that  this  case  is 
an  instance  of  a  mixed  general  infection  with  gonococcus  plus 
staphylococcus. 

Bergmann  ("  Gonitis  gonorrhceica  mit  Coccen,"  St.  Petersburger 
med.  Wochenschrift,  1885,  No.  35)  found  gonococci  in  pus  removed 
from  a  knee-joint  of  a  patient  suffering  from  gonorrhoea,  three 
weeks  after  the  beginning  of  the  urethritis. 

Haslund  ("  Beitrag  zur  Pathogenese  des  gonorrhoeischen  Rheu- 
matism us,"  Vierteljahrssehrift  f.  Derm.  u.  Syph.,  B.  ix.  p.  359),  on 
the  other  hand,  was  unable  to  find  the  specific  cocci  of  gonorrhoea 
in  eleven  cases  of  synovitis  in  gonorrhoea  patients. 

Hoffa  ("  Bacteriologische  Mitth.  aus  der  chir.  Kliuik  des  Prof. 
Maas,  Wiirzburg,"  Fortschritte  der  Mediein,  B.  x.  p.  75)  found  no 
gonococci  in  a  purulent  synovitis  occuring  in  a  patient  suffering 
from  gonorrhoea,  but  in  two  cases  in  which  bubo  formed  he  found 
staphylococcus  pyogenes  albns  and  aureus  in  the  pus  of  the  abscesses, 


238  GONORRHOEA. 

but  no  gonococci.  These  were  undoubtedly  cases  in  which  suppura- 
tion in  the  glands  was  caused  by  a  mixed  infection.  Smirnoff 
(Wratch,  1886,  No.  31)  examined  the  sero-purulent  contents  re- 
moved from  the  knee-joint  by  aspiration,  in  a  patient  twenty-eight 
years  of  age,  six  weeks  after  gonorrhoeal  infection  and  two  weeks 
after  the  commencement  of  the  joint  affection,  and  found  numerous 
clusters  of  gonococci  within  the  pus-corpuscles.  Afauasieff  made 
similar  observations. 

Sahli  has  recorded  a  very  interesting  case  of  gonorrhoeal  meta- 
stasis of  the  skin.  In  a  patient  who  for  two  months  had  suffered 
from  gonorrhoea,  there  appeared  two  abscesses,  as  large  as  a  man's 
fist,  situated  in  the  region  of  the  knee-joint.  On  incision  a  large 
quantity  of  sero-sanguinolent  pus  escaped.  Microscopical  examina- 
tion revealed  the  presence  of  typical  gonococci,  imbedded,  as  usual, 
within  pus-corpuscles. 

Some  pathologists,  among  them  Watson  Cheyne  ("  Lectures  on 
Suppuration  and  Septic  Diseases,"  Brit.  Med.  Journ.,  February  15, 
March  3,  10,  1888),  assert  that,  when  in  cases  of  gonorrhoea  sup- 
purative  adenitis  and  para-adenitis  in  the  inguinal  glands  take 
place,  pus-microbes  are  present  in  the  pus,  and  the  suppuration 
must  be  considered  as  the  consequence  of  a  mixed  infection. 

DIAGNOSTIC  VALUE  OF  THE  GONOCOCCUS. — Neisser,  Bumrn, 
Bockhardt,  Eschbaum,  ISTewberry,  Campona,  Aufrecht,  Schwarz, 
Lundstrom,  Weiss,  Ehrlich,  Brieger,  Hartdegen,  and  others  have 
never  failed  in  finding  the  gonococcus  present  in  gonorrhoeal  dis- 
charges. The  best  ophthalmologists  rely  upon  its  presence  in  differ- 
entiating between  specific  and  simple  conjunctivitis.  Only  a  few 
authorities  have  arrayed  themselves  against  Neisser's  claim. 

Sanger  ("  Gonorrhoeal  Disease  of  the  Uterine  Appendages  and 
its  Operative  Treatment,"  Archiv  f.  Grynakologie,  B.  xxv.  Heft  1) 
states  that  the  hope  aroused  by  the  discovery  of  Neisser,  that  in  the 
gonococcus  we  should  find  the  means  of  diagnosing  chronic  gonor- 
rhoea, had  proved  to  be  in  vain,  and  holds  it  to  be  an  established 
fact  that  gonorrhoea  can  exist  without  the  demonstrable  presence  of 
gonococci.  The  absence  of  the  gonococcus  proved  nothing  against 
the  gonorrhoeal  nature  of  the  disease ;  whilst  the  presence  of  diplo- 
cocci,  in  view  of  the  occurrence  of  non -pathogenic  forms,  did  not 
prove  the  gonorrhoeal  nature  of  the  disease.  If  the  cocci  cannot  be 
found,  they  may  have  been  somewhere  broken  up,  while  a  ferment 
produced  by  them  may  still  be  active ;  or  they  are  absent  from  the 
secretion  while  present  in  the  tissues;  or  there  exists — and  this 
would  render  the  high  degree  of  infectiousuess  of  a  comparatively 
trifling  amount  of  secretion  in  latent  gonorrhoea  the  most  intelli- 
gible— a  permanent  form  (Dauer-form)  of  the  gonococcus  not  yet 
discovered. 


DIAGNOSTIC    VALUE    OF    THE     GOXOCOCCUS.         239 

Eugen  Frankel  ("Bericht  iiber  erne  bei  Kindern  beobachtete 
Endemic  infektioser  Kolpitis,"  Virchow's  Archiv,  B.  xcix.  p.  251) 
claimed  to  have  found  a  diploeoccus  in  the  secretions  of  non-gonor- 
rhoeal  colpitis  in  children  which  could  not  be  distinguished  from 
the  gonococcus  of  Neisser.  He  therefore  argued  that  for  diagnostic 
purposes  the  simple  presence  of  the  microbe  could  not  be  relied 
upon,  and  cultivation  and  inoculation  experiments  became  necessary 
in  order  to  differentiate  between  the  specific  and  non-specific  diplo- 
coccus. Later,  after  resorting  to  another  method  of  staining,  he 
satisfied  himself  that  the  diplococcus  was  identical  with  Neisser's 
gonococcus. 

Sinety  and  Henneguy  have  made  special  observations  in  reference 
to  the  presence  of  the  gonococcus  in  the  pus  of  gonorrhceal  urethritis 
in  the  female  and  found  it  present  only  in  cases  in  which  the  urine 
was  of  alkaline  reaction,  while  they  failed  to  find  it  when  the  urine 
was  acid. 

Pott  (Archiv  f.  G-ynakologie,  B.  xxxii.  Heft  3)  has  examined  96 
cases  of  purulent  vulvo-vaginitis  in  children,  more  than  one-half 
of  whom  were  under  five  years  of  age.  He  believes  that  they  were 
all  the  result  of  some  specific  infection.  Small  endemics  occurred 
from  the  infection  of  several  children  in  the  same  family,  through 
the  medium  of  soiled  clothing,  sponges,  etc.  The  writer  has  only 
observed  three  cases  of  gonorrhceal  infection  by  direct  communica- 
tion of  the  virus.  Bacteriological  examination  of  the  discharge 
usually  revealed  the  presence  of  the  specific  microbe  of  gonorrhoea. 
In  the  discussion  of  this  paper,  Prochownik  stated  that  he  had  found 
the  cocci  in  17  out  of  21  cases  of  vulvo-vaginitis  in  children.  In 
all  of  the  cases  urethritis  was  a  prominent  symptom.  A  girl,  three 
and  a  half  years  of  age,  that  came  under  the  care  of  Sanger  devel- 
oped intense  peritonitis  in  consequence  of  an  attack  of  gonorrhoea. 
Sanger  is  of  the  opinion  that  cases  of  pyosalpinx  and  old  localized 
pelveo-peritonitis  in  young  virgins  might  possibly  be  referred  to 
gonorrhoea  contracted  in  childhood  through  indirect  infection. 

Spaeth  (Munchener  med.  Wochenschrift,  1889)  examined  the  pus 
in  21  cases  of  vulvo-vaginitis  occurring  in  girls  between  three  and 
eleven  years  old,  and  found  gouococci  in  14.  In  the  non-specific 
catarrh  the  inflammation  never  implicated  the  mucous  membrane  of 
the  urethra.  In  adult  females  affected  with  gonorrhoea  the  greatest 
number  of  the  specific  microbes  is  always  found  in  the  pus  from 
the  urethra.  In  children  it  is  not  always  easy  to  discover  the 
source  of  infection.  In  11  of  the  above  cases  the  mother  had  gon- 
orrhoea;  in  2,  the  father;  in  3  only  had  the  child  been  violated. 
In  children  the  disease  seldom  extends  to  the  uterus  and  tubes, 
although  a  few  cases  of  gonorrhoeal  pyosalpinx  have  been  reported. 

Steinschneider  (Qentralblatt  f.  d.  med.  Wissensch.,  1890,  No.  39) 


240  GONORRHCEA. 

regards  Gram's  method  of  staining  as  necessary  to  make  the  micro- 
scopic examination  of  gonorrhoea!  pus  of  diagnostic  value,  as  the 
gouococcus  is  not  stained  by  this  method,  while  nearly  all  other 
diplocoeci  found  in  the  urethra  are  colored  thereby. 

These  conclusions,  which  agree  with  those  of  Roux,  are  the 
result  of  the  examination  of  86  patients  with  acute  and  chronic 
gonorrhoea.  The  almost  entire  certainty  of  this  test  is  rendered 
absolute  by  the  observation  of  the  further  characteristic  of  the 
gonococci,  namely,  that  they  are  found  within  the  pus-corpuscles. 

Sternberg  (The  Medical  News,  January  20,  1883)  cultivated  a 
micrococcus  from  gonorrhoeal  discharges  in  bouillon  which  in  its 
morphology  resembled  the  gonococcus  described  by  Neisser.  He 
made  numerous  inoculation  experiments  in  animals  and  a  few  in 
man  with  only  negative  results.  Subcutaneous  injections  of  a  pure 
culture  also  proved  harmless.  He  came  to  the  conclusion  that  the 
micrococcus  which  he  found  corresponded  to  the  micrococcus  urea3 
of  Cohn  ;  the  pathogenic  eifect  of  which  has  been  shown  to  be  the 
cause  of  the  alkaline  fermentation  of  urine  (Pasteur). 

Leistikow  (Deutsche  Medicinal-Zeitung,  September  7,  1882)  has 
observed  that  during  the  first  stage  of  gonorrhoea,  when  the  dis- 
charge is  thick  and  abundant,  but  few  gonococci  could  be  found. 
They  were  found  abundant  in  the  thin  and  scanty  secretion  of  the 
later  stages,  sometimes  even  when  the  disease  had  existed  for  a 
year.  All  authorities  who  have  studied  the  relations  of  the  gono- 
coccus to  gonorrhoea  with  the  greatest  care,  insist  that,  for  diagnostic 
purposes,  it  is  not  only  necessary  to  demonstrate  its  presence,  but 
to  ascertain  its  intra-cellular  location  and  the  manner  in  which  this 
microbe  arranges  itself  in  groups  in  the  protoplasm  of  the  cell  be- 
tween the  nucleus  and  the  envelope  of  the  cell,  and  these  conditions 
should  be  studied  with  the  greatest  care  in  all  medico-legal  cases  in 
which  a  positive  opinion  must  rest  on  a  microscopical  examination 
of  the  secretion. 


CHAPTEE   XXII. 

SYPHILIS. 

THE  infectious  microbic  nature  of  syphilis  is  so  evident  that  no 
one  for  a  moment  would  dare  to  question  it,  and  yet  with  all 
modern  improvements  for  bacteriological  research  and  the  prevalence 
of  this  affection  at  all  times,  and  all  over  the  world,  it  is  strange 
that,  so  far,  it  has  not  been  possible  to  furnish  positive  and  con- 
vincing proof  of  the  existence  of  a  definite,  specific  microorganism 
in  all  syphilitic  lesions,  and  to  demonstrate  its  etiological  relation 
to  this  disease.  It  is  interesting  and  profitable  to  know  what  has 
been  done  during  the  last  few  years  in  the  bacteriological  study  of 
syphilitic  lesions,  and  although  the  claims  which  have  been  made 
are  in  all  probability  unfounded,  I  will  give  a  brief  resume  of  the 
literature  on  this  subject. 

In  1884  Lustgarteu  (Wiener  med.  Woehenschrift,  1884,  No.  47) 
announced  that  he  had  found  a  bacillus  in  two  cases  of  initial 
sclerosis  and  in  a  syphilitic  gumma,  for  which  he  claimed  specific 
pathogenic  properties.  Nearly  at  the  same  time,  and  without 
knowledge  of  Lustgarteu's  work,  Doutrelepout  found  a  bacillus  in  a 
primary  hard  chancre,  two  broad  condylornata,  and  in  one  case  of 
syphilitic  papular  eruption  of  the  skin,  which  resembled  closely  the 
bacillus  of  tuberculosis.  He  found  it  difficult  to  stain  this  bacillus, 
but  finally  succeeded  with  geutian-violet.  In  the  beginning  of  the 
year  1885,  Lustgarten  (''Die  Syphilisbacillen,"  Mit.  4  Tafeln, 
Wiener  med.  Jahrb.,  1885)  published  his  second  paper,  in  which  he 
gave  an  accurate  description  of  the  bacillus  and  the  results  of  a 
more  extended  investigation  of  the  subject.  He  had  in  the  mean- 
time examined  numerous  specimens  of  syphilitic  lesions,  and  as  he 
had  invariably  been  able  to  demonstrate  the  presence  of  the  bacillus 
in  them  and  its  absence  in  two  soft  chancres,  he  expressed  his  firm 
conviction  that  the  bacillus  was  the  specific  cause  of  the  disease. 

DESCRIPTION  OF  LUSTGARTEN ?s  BACILLUS  OF  SYPHILIS. — The 
bacilli  are  rods  3  to  4  micromillimetres  in  length,  and  0.88  micro- 
millimetre  in  thickness,  resembling  somewhat  the  bacilli  of  leprosy 
and  tuberculosis.  The  rods  are  not  straight,  but  somewhat  curved, 
or  S-shaped.  After  staining,  light  oval  spots  were  seen  within 
their  protoplasm  which  were  thought  to  be  spores.  The  bacilli 
were  never  seen  free,  but  were  always  found  in  the  interior  of 


242  SYPHILIS. 

nucleated  cells  which  are  more  than  double  the  size  of  leucocytes. 
The  bacilli  have  been  observed  in  the  discharge  of  the  primary 
lesion,  and  in  the  hereditary  affections  of  tertiary  gummata. 

STAINING. — Lustgarten'a  Method.  Sections  are  placed  for  from 
twelve  to  twenty-four  hours  in  the  following  solution  at  the  ordi- 
nary temperature  of  the  room,  and  finally  the  solution  is  warmed 
for  two  hours  at  60°  C.  (140°  F.)  : 

Concentrated  alcoholic  solution  of  gentian-violet        .       11  parts. 
Aniline  water         ........     100      " 

The  sections  are  then  placed  for  a  few  minutes  in  absolute  alcohol, 
and  from  this  transferred  to  a  1.5  per  cent,  solution  of  permanganate 
of  potassium.  After  ten  minutes  they  are  immersed  for  a  moment 
in  a  pure  concentrated  solution  of  sulphurous  acid.  If  the  section 
is  not  completely  decolorized,  immersion  in  the  alcohol  and  in  the 
acid  must  be  repeated  three  or  four  times.  The  sections  are  finally 
dehydrated  with  absolute  alcohol,  cleared  with  clove-oil,  and 
mounted  in  Canada  balsam.  Giacomi  has  simplified  and  improved 
this  method.  He  immerses  cover-glass  preparations  by  staining 
them  for  a  few  moments  in  a  solution  of  fuchsin,  after  which  they 
are  washed  in  water  to  which  a  few  drops  of  a  solution  of  chloride 
of  iron  have  been  added.  Complete  decolorization  is  effected  in  a 
concentrated  solution  of  chloride  of  iron. 

Doutrelepont  and  Schiitz  obtained  good  results  by  staining  in  a 
one  per  cent,  gentian  solution,  decolorizing  in  a  solution  of  nitric 
acid  1:15,  and  after-staining  with  safranin ;  after  which  they  are 
dehydrated  in  a  sixty  per  cent,  solution  of  alcohol,  cleared  in  clove- 
oil,  and  mounted  in  Canada  balsam.  After  this  process  the  bacilli 
are  stained  blue  and  the  tissues  red. 

Gottstein  immersed  the  sections  for  twenty-four  hours  in  fuchsin 
solution,  after  which  they  were  washed  in  water  and  transferred 
into  pure  or  diluted  tincture  of  chloride  of  iron,  dehydrated  in 
alcohol,  and  cleared  up  in  oil  of  cloves  or  xylol,  when  they  are 
ready  to  be  embedded  in  Canada  balsam.  This  method  stains  the 
bacilli  a  red  or  dark  violet  color. 

CULTIVATION  EXPERIMENTS. — Lustgarten's  cultivation  experi- 
ments did  not  succeed.  Few  attempts  to  reproduce  the  bacillus 
upon  different  nutrient  media  have  yielded  positive  results.  Klebs 
succeeded  best  in  cultivating  them  upon  a  gelatin  prepared  from 
the  bladder  of  a  kind  of  sturgeon  (Hansenblasen-gallerte)  found  in 
some  of  the  rivers  of  Russia.  Inoculations  of  gelatin  kept  at  the 
ordinary  temperature  of  the  room  produced,  after  thirty-seven  days, 
around  the  implanted  piece  of  tissue  a  grayish-yellow  culture.  In 
one  instance  the  same  culture  medium  was  inoculated  with  the 
blood  of  an  infected  monkey,  when  on  the  fifth  day  a  brownish 


PLATE    XIII. 


-\  / 


\ 


Syphilis  bacilli  from  a  papule,  after  a  preparation  from  Lustgarten. 
2500  diam. 


BACTERIOLOGICAL    STUDY    OF    SYPHILIS.  243 

zone  had  formed  around  the  streak  made  by  the  needle,  which  on 
microscopical  examination  was  seen  to  be  composed  exclusively  of 
small  bacilli.  Embedded  in  the  culture,  granules  were  also  found, 
which  were  thought  might  be  spores.  Similar  results  have  since 
been  obtained  by  Martineau  and  Hammonic  (Les  Baderies,  par 
Coruil  et  Babes,  p.  774)  and  Birch-Hi  rschfeld  (Centralblatt  f.  d. 
med.  Wiss.,  1882,  Nos.  33,  44),  who  cultivated  the  bacillus  from 
the  primary  lesion,  condylomata,  and  gummata  of  internal  organs. 

INOCULATION  EXPERIMENTS. — The  transmission  of  syphilis  to 
animals  by  implantation  of  syphilitic  tissue,  or  by  inoculations  with 
cultures,  has,  so  far,  not  met  with  uniform  success,  as  it  has  been 
found  difficult  to  find  animals  susceptible  to  syphilitic  infection. 

Kleb's  experiments  on  monkeys  yielded  positive  results.  Mar- 
tineau and  Hammonic  experimented  on  the  same  animal,  and  pro- 
duced the  disease  by  inoculation  with  a  pure  culture.  They  observed 
twenty-eight  days  after  inoculation  of  the  prepuce  two  indurations 
which  were  followed  by  general  secondary  symptoms.  In  one  case 
in  which  Klebs  used  a  culture  for  inoculation  an  abscess  formed,  and 
the  animal  remained  apparently  well  until  the  seventh  week,  when  a 
granulation-swelling  formed  at  the  base  of  the  upper  jaw  which 
ulcerated,  and  from  this  point  a  cheesy  infiltration  extended  to  the 
base  of  the  skull ;  the  same  deposits  were  found  between  the  base 
of  the  skull  and  the  dura  mater.  From  the  abscess  which  still 
contained  cheesy  masses  lymphatic  infection  had  taken  place,  and 
the  glands  also  contained  cheesy  material.  No  miliary  tuberculosis 
could  be  found.  Bacilli  were  found  in  the  cheesy  material  which 
were  identical  with  those  contained  in  the  inoculation  material.  In 
another  case  a  piece  of  tissue  from  a  hard  chancre  was  implanted 
under  the  skin  of  one  of  the  posterior  extremities.  Six  weeks  after 
the  implantation  general  and  febrile  symytoms  supervened,  attended 
by  a  papular  eruption  on  the  forehead  and  face.  Death  occurred 
five  months  after  inoculation,  and  at  the  post-mortem  syphilitic 
lesions  were  found  in  the  skull  and  lungs. 

Bacteriological  and  Experimental  Study  of  Syphilis. 

Doutrelepont  and  Schiitz  ("  Die  Bacillen  bei  Syphilis,"  Deutsche 
med.  Wochenschrift,  1885,  No.  9)  are  more  reserved  in  their  state- 
ments than  Lustgarten  in  reference  to  the  causation  of  syphilis  by 
the  bacillus  just  described.  In  regard  to  the  uniform  presence  of 
a  bacillus  in  syphilitic  lesions  they  concur  in  the  views  advanced 
by  Lustgarten.  They  found  the  bacillus  between  and  within  cells. 
They  consider  it  as  the  probable  cause  of  syphilis,  but  they  thought 
that  further  proof  must  be  furnished  by  culture  and  inoculation 
experiments  before  this  question  could  be  definitely  settled. 


244  SYPHILIS. 

Doutrelepont  found  the  bacillus  taken  from  the  blood  near  a 
syphilitic  lesion  of  the  skin,  and  from  a  syphilitic  primary  sclerosis 
of  the  upper  lip  produced  a  feeble  culture  upon  solidified  hydrocele 
fluid. 

Matterstock  (Sitzungsbericht  d.  pliys.-med.  G-esellschaft  zu  Wurz- 
burg,  1885,  und  Ueber  Bacillen  bei  Syphilis,  Wiirzburg,  1885),  after 
a  careful  examination  of  100  sections  and  150  specimens  of  secre- 
tions from  syphilitic  lesions,  supported  in  the  main  the  views  held 
by  Lustgarten,  and  places  great  importance  upon  microscopical 
examination  of  syphilitic  products  as  a  diagnostic  measure.  Con- 
jointly with  Bitter,  of  Osnabriick,  he  found  the  disintegrated  bacilli 
described  by  Doutrelepont  in  the  shape  of  granular  masses,  which 
outlined  the  size  and  shape  of  the  bacilli.  He  often  saw  the  bacilli 
between  the  cells  and  the  connective-tissue  fibrillse.  He  states  that 
the  bacillus  is  not  present  in  large  numbers  in  the  specimens,  and 
unless  carefully  searched  for  may  not  be  found.  As  it  can  be  found 
in  the  lesions  of  all  three  stages  of  the  disease,  he  asserts  that  its 
etiological  importance  can  be  no  longer  doubted,  even  although 
cultivation  and  inoculation  experiments  have  so  far  not  furnished 
the  crucial  test.  Later  the  same  author  found  similar  bacilli  in  the 
secretions  of  the  genital  organs  in  patients  in  whom  syphilis  could 
be  excluded  with  certainty. 

Markuse  ( Vierteljahrsschrift  fur  Dermat.  und  Syph.,  1888)  on 
examining  109  cases  found  Lustgarten's  bacilli  in  10  of  23  cases  of 
hard  chancre,  in  43  of  57  of  anal  condylomata,  and  once  in  19  cases 
of  papules  about  the  mouth  examined.  In  8  gummata  and  2  pus- 
tular syphilides  no  bacilli  were  found.  Smegma  bacilli  wrere  found 
in  125  cases  examined.  They  differ  from  the  bacilli  of  syphilis  in 
being  more  easily  decolorized  by  acids. 

Andromico  ("  Ueber  die  parasitare  Genese  der  Syphilis,"  Viertel- 
jahrsschrift /.  Derm.  u.  Syph.9  1886,  p.  475)  claims  to  have  culti- 
vated from  a  flat  nodule  of  the  skin  in  a  syphilitic  patient,  cocco- 
bacteria  which,  injected  under  the  skin  of  a  rabbit,  produced  a 
typical  indurated  ulcer,  followed  by  glandular  infiltration.  He 
also  inoculated  a  cat  with  fluid  contents  of  a  syphilitic  pemphigus 
with  the  result  of  producing  a  hard,  painless  swelling  followed  by 
a  papular  eruption  of  the  skin,  and  loss  of  hair  of  the  skin  covering 
the  abdomen.  The  fluid  injected  and  the  syphilitic  lesions  in  the 
animal  contained  the  same  bacteria  which  he  had  cultivated  from 
the  syphilitic  nodule  of  the  skin. 

Doutrelepont  ("Ueber  die  Bacillen  bei  Syphilis,"  Vierteljahrs- 
schrift f.  Derm.  u.  Syph.,  1887,  p.  101),  after  more  extended  obser- 
vations, has  come  to  the  positive  conclusion  that  bacilli  are  always 
present  in  syphilitic  lesions,  and  even  in  the  blood  of  patients  suf- 


BACTEEIOLOGICAL    STUDY    OF    SYPHILIS.  245 

fering  from  syphilis,  and  insists  that  in  spite  of  the  discovery  of  the 
bacillus  of  smegraa  they  must  be  regarded  as  the  cause  of  syphilis. 

Zeissi  ("  Untersuchungen  uber  den  Lustgarten'schen  Bacillus  in 
Syphilisproducten  und  Secreteu  derselben,"  Wiener  med.  Presse, 
1885,  No.  48)  examined  sections  from  nine  cases  of  initial  sclerosis 
for  bacilli,  and  found  them  present  only  in  one,  and  in  this  one, 
only  two  were  to  be  seen.  Baumgarten  readily  detected  Lustgar- 
ten's  bacillus  in  a  specimen  taken  from  a  hard  chancre  by  resorting 
to  De  Giacomi's  method  of  staining  after  he  had  failed  in  numerous 
instances  with  Lustgarten's  method. 

Haberkorn  claims  to  have  found  in  the  blood  of  syphilitic 
patients  a  microorganism  which  he  describes  as  a  round,  oval,  or 
short  cylindrical-shaped  spore  of  darkened  color,  0.001  to  0.002 
millimetre  in  diameter,  which  is  also  found  in  close  proximity,  or 
adherent  to  white  blood-corpuscles.  He  also  claims  to  [have 
cultivated  this  microbe. 

Marcus  (These  de  Paris,  Anncdes  de  Derm,  et  Syph.,  1885)  dis- 
covered another  microbe  which  he  believed  to  be  the  cause  of 
syphilis.  He  found  in  syphilitic  lesions  cocci  arranged  in  groups 
of  from  six  to  seven,  which  could  be  readily  stained  with  gentian- 
violet.  They  resist  the  action  of  alcohol,  and  are  easily  deprived  of 
their  color  in  acidulated  alcohol.  He  made  successful  cultivations, 
but  his  inoculation  experiments  yielded  only  negative  results. 

Another  bacillus  which  was  supposed  to  be  the  cause  of  syphilis 
was  described  by  Eve  and  Liugard  (On  a  Bacillus  Cultivated 
from  the  Blood  and  from  Diseased  Tissues  in  Syphilis,  1886). 
This  bacillus  contained  spores  and  was  readily  cultivated.  It 
appeared  in  the  form  of  rods  somewhat  variable  in  length,  which 
on  staining  showed  that  the  different  segments  were  unequally 
stained.  The  most  successful  results  in  staining  were  obtained  with 
Humbolt-red,  in  aniline  oil,  and  decolor ization  in  alcohol.  Gram's 
method  was  also  found  efficient,  while  Lustgarten's  yielded  only 
negative  results.  The  cultures  grew  upon  solid  blood  serum  or 
hydrocele  fluid  and  agar-agar. 

Disse  and  Taguchi  ("  Ueber  das  Coutagium  der  Syphilis," 
Deutsche  med.  Wockenschrift,  1885,  No.  48,  and  same,  1886,  No. 
14)  examined  the  blood  of  patients  suffering  from  secondary  syphi- 
lis, and  found  in  it  almost  constantly  cocci  of  one  micromillimetre 
in  diameter,  isolated,  or  in  colonies  between  the  blood  corpuscles. 
The  cultures  upon  different  nutrient  media  appeared  as  grayish- 
white  masses.  All  culture  media  with  the  exception  of  solid 
blood  serum  were  liquefied  by  them,  and  it  is  the  first  time  that 
we  have  an  account  of  the  liquefaction  of  agar-agar  by  microbes. 
In  the  cultures  the  microbes  appear  in  pairs  which  give  them  the 
appearance  of  short  rods  with  a  light  space  in  the  middle  at  the 


246  SYPHILIS. 

point  of  junction  of  the  two  cocci.  They  exhibited  active  move- 
ments, and  reproduction  was  seen  to  take  place  by  simple  segmen- 
tation. Gram's  method  of  staining  proved  most  successful.  Iso- 
lated cocci,  the  authors  believe,  exist  in  the  blood  of  patients  the 
subject  of  latent  syphilis,  and  in  cultures  made  from  them  the 
diplococcus  appears.  With  a  pure  culture  seven  rabbits,  two  sheep, 
five  dogs,  and  one  white  mouse  were  inoculated.  Under  strict 
antiseptic  precautions  the  microbes  were  introduced  into  the  sub- 
cutaneous tissue  through  a  minute  incision.  Diplococci  were  found 
in  the  blood  of  the  dogs  and  rabbits  after  ten  days,  in  the  sheep 
after  three  weeks,  and  their  presence  remained  constant  for  several 
months.  Among  the  dogs  were  four  females ;  two  of  them  were 
pregnant  at  the  time  of  inoculation,  and  all  of  the  pups  died  soon 
after  they  were  born.  Some  of  the  inoculated  animals  died  at  dif- 
ferent times,  and  the  others,  with  the  exception  of  two,  were  killed 
in  from  two  to  eight  months  after  inoculation.  In  none  of  the 
animals  could  any  infection  of  the  skin  or  mucous  membranes 
be  found.  Induration  at  the  point  of  inoculation  was  noticed 
in  only  one,  and  it  disappeared  eighteen  days  after  the  inoculation. 
In  all  of  the  animals  characteristic  pathological  changes  were  found 
in  the  heart,  lungs,  liver,  and  kidneys.  The  authors  believe  that 
the  syphilitic  virus  in  animals,  like  in  man,  acts  upon  the  blood- 
vessels, only  that  in  animals  the  morbid  changes  take  place  in 
other  organs.  In  animals  the  vessels  of  the  skin  remain  exempt, 
while  the  vessels  in  the  heart,  lungs,  liver,  and  kidneys  are  diseased. 
Quite  frequently  the  vessels  of  the  brain  were  also  found  diseased, 
but  very  seldom  the  vessels  of  the  intestines.  Syphilitic  gummata 
were  also  found  less  frequently  than  in  man.  The  authors  claim 
that  the  microbes  live  in  the  circulating  blood,  and  they  found 
them  in  great  abundance  in  the  affected  tissue,  in  which  they 
appeared  to  have  only  a  limited  existence.  They  believe  that 
syphilis  becomes  latent  as  soon  as  the  cocci  cease  to  grow. 

From  the  above  extracts  of  the  current  literature  on  the  etiology 
of  syphilis,  it  can  be  seen  that  different  microbes  have  been  found 
in  the  blood  and  tissue  lesions  of  patients  suffering  from  syphilis, 
and  that  the  discoverers  of  each  of  them  claimed  to  have  found  the 
microbic  cause  of  syphilis.  So  far,  no  uniform  results  have  been 
obtained,  and  it  must  be  left  for  future  research  to  discover  a  new 
microbe,  or  to  substantiate  some  one  of  the  claims  made  in  the  past. 
This  much  we  can  say  for  Lustgarten,  that  he  has  at  least  pointed 
out  the  proper  method  for  future  investigations. 

The  Bacillus  of  Smegma. 

Soon  after  the  publication  of  Lustgarten's  second  paper,  Tavel 
(Archiv  de  physiol.  et  path.,  No.  7,  1885)  announced  that  he  had 


SYPHILITIC     LESIONS    WITH    PUS    MICROBES.        247 

found  a  bacillus  in  the  smegma  and  secretions  of  the  mucous  mem- 
branes of  the  external  genital  organs,  which  in  shape  and  its  reac- 
tion to  staining  material  proved  identical  with  the  bacillus  described 
by  Lustgarten.  Klemperer,  from  his  own  observations,  came  also 
to  the  conclusion  that  the  smegma  bacillus  resembled  Lustgarten's 
bacillus,  that  their  identity  appeared  more  than  probable.  Both 
Tavel  and  Klemperer  mention  as  a  distinguishing  feature  between 
the  smegma  bacillus  and  the  bacillus  of  tuberculosis,  that  the 
former  is  completely  decolorized  by  washing  the  dried  and  stained 
preparation  for  a  minute  and  a  half  in  a  33J  per  cent,  solution  of 
nitric  acid,  and  afterward  for  half  a  minute  in  absolute  alcohol.  In 
specimens  thus  treated,  the  bacilli  disappear,  while  the  tubercle 
bacilli  similarly  treated  remain  deeply  stained. 

In  September,  1885,  Doutrelepont  published  his  observations  on 
the  smegma  bacillus,  wherein  he  corroborates  Tavel's  observations 
(TavePs  "  Zur  Geschichte  der  Smegmabacillen/'  Centralblatt  f. 
Bact.  u*  Parasitenkunde,  B.  i.,  No.  23). 

Secondary  Infection  of  Syphilitic  Lesions  with  Pus  microbes. 

Kassowitz  and  Hochsinger  ("  Ueber  eineu  Mikro-organismus  in 
den  Gewheben  hereditar  syphil.  Kinder,"  Wiener  med.  Blatter, 
B.  ix.,  1886)  reported  during  the  early  part  of  the  year  1886  that 
they  had  found,  by  means  of  a  modification  of  Gram's  method  of 
staining,  a  chain  coccus  in  the  contents  of  pemphigus  bullse,  the 
bones,  liver,  pancreas,  lungs,  and  thymus  gland  of  five  syphilitic 
children  who  had  died  soon  after  birth.  The  microbes  were  found 
within  the  vessels  and  the  para  vascular  spaces  ;  the  finer  capillaries 
were  sometimes  seen  to  be  completely  filled  with  .them.  The  cocci 
were  found  in  close  contact  with  the  red  blood-corpuscles,  but 
never  in  their  interior,  or  within  other  cells.  They  were  only 
found  in  organs  in  which  syphilitic  lesions  could  be  detected  by 
naked-eye  appearances,  or  by  microscopical  examination,  and  could 
never  be  found  in  the  same  places  in  non-syphilitic  children. 
From  the  streptococcus  of  erysipelas  these  microbes  differed  as 
they  were  found  either  within  or  in  the  immediate  vicinity  of 
bloodvessels,  and  from  the  streptococcus  pyogenes  in  that  they  did 
not  cause  suppuration.  The  authors  do  not  claim  that  this  microbe 
is  the  cause  of  syphilis,  but  look  upon  this  discovery  as  an  import- 
ant episode  in  the  study  of  syphilis. 

Kolisko  has  examined  the  bodies  of  numerous  syphilitic  children 
who  died  one  or  two  days  after  birth,  and  was  unable  to  find  this 
streptococcus  or  any  other  microorganism.  In  one  case  in  which 
the  child  lived  for  fourteen  days,  and  had  suffered  from  furunculo- 
sis,  he  found  a  streptococcus  which  he  took  for  the  streptococcus 


248  SYPHILIS. 

pyogenes.  He  believed  that  this  microbe  had  entered  the  body 
through  an  open  pemphigus  blister,  the  umbilicus,  or  had  been 
derived  from  the  furuncles.  In  another  case  in  which  he  found 
the  same  microorganism  in  the  liver,  he  obtained  a  pure  culture  of 
the  streptococcus  pyogenes  from  blood  taken  from  the  liver. 

Chotzen  ( Vierteljahrsschrift  f.  Derm.  u.  Syphilis,  1887,  S.  109) 
states  that  in  searching  for  the  same  microbe,  in  Neisser's  clinique, 
it  was  found  once  in  bone,  five  times  in  the  skin,  four  times  in  the 
liver,  once  in  the  mucous  membrane  of  the  intestine;  in  the  last- 
mentioned  organ  the  microbe  was  found  in  great  abundance,  not  in 
the  vessels,  but  in  the  paravascular  and  lymph  spaces.  In  bone  it 
was  found  where  syphilitic  lesions  are  usually  met  with.  As  the 
result  of  his  observations  he  looks  upon  the  streptococcus  only  as 
an  accidental,  and  not  as  an  essential,  condition  of  hereditary  syph- 
ilis. In  cases  of  acquired  syphilis  it  was  never  found.  As  this 
streptococcus  must  be  different  from  the  microbe  of  erysipelas  and 
of  suppuration,  it  still  remains  an  open  question  as  to  its  relation 
to  syphilitic  infection.  From  a  hypothetical  standpoint  he  regards 
the  presence  of  the  streptococcus  as  an  evidence  of  a  mixed  infec- 
tion, and  believes  that  it  produces  death  by  giving  rise  to  sepsis. 
The  presence  of  the  coccus  in  the  medullary  tissue  of  the  epiphy- 
seal  extremities  of  the  long  bones  would  furnish  an  explanation 
regarding  the  frequency  with  which  lesions  are  found  here  in  chil- 
dren suffering  from  hereditary  syphilis.  As  points  of  entrance  of 
the  streptococcus  he  enumerates  coryza  and  inflammation  of  the 
naso-pharyngeal  space. 

Doutrelepont  ("  Streptokokken  und  Bacillen  bei  hereditarer  Syph- 
ilis,'7 Centralblatt  f.  Bad.  u.  Parasitenhmde,  B.  ii..  No.  13)  agrees 
with  Chotzen  in  regard  to  the  character  and  etiological  significance 
of  the  streptococcus  found  in  children  suffering  from  congenital 
syphilis.  He  has  found  it  in  the  papular  eruptions  of  the  skin, 
and  believes  that  it  enters  the  lymph  spaces  here,  and  through  these 
channels  reaches  the  general  circulation  and  distant  organs.  The 
frequency  with  which  suppuration  in  bones  and  other  organs  is  met 
with  in  children  soon  after  birth,  and  sometimes  in  utero,  would 
suggest  that  the  secondary  infection  results  from  the  introduction, 
sometimes  through  the  maternal  circulation,  at  others  through 
lesions  after  birth  of  pus  microbes,  which  become  localized  in 
organs  the  seat  of  syphilitic  lesions,  where,  in  the  course  of  time, 
suppuration  takes  place.  The  presence  of  an  abundance  of  pus 
microbes  may  destroy  life  by  sepsis  before  a  sufficient  length  of 
time  has  elapsed  for  them  to  manifest  their  specific  pathogenic 
properties  on  the  tissues. 


CHAPTEE    XXIII. 

ON  THE  ALLEGED  MICROBIC  ORIGIN  OF  TUMORS. 

SMALL,  round-celled  sarcoma  resembles  in  its  histological  struc- 
ture grauulomata  so  closely  that  under  the  microscope  it  would  be 
impossible  to  make  a  positive  differential  diagnosis  between  the 
two;  at  the  same  time  all  malignant  tumors  in  their  clinical  be- 
havior have  so  many  things  in  common  with  infective  swellings 
that  it  does  not  appear  strange  that  the  microbic  nature  of  sarcoma 
and  carcinoma  has  been  suspected  for  a  long  time,  and  that  during 
the  recent  strides  which  the  modern  science  of  bacteriology  has 
made,  this  subject  has  been  studied  by  the  most  improved  methods 
of  investigation. 

The  veteran  surgeon  and  pathologist,  Sir  James  Paget  (Lancet, 
1887,  No.  19),  not  long  ago  called  attention  to  the  resemblance 
existing  between  cancer  and  benign  tumors  on  the  one  hand,  and 
specific  and  micro-parasitic  affections  on  the  other.  He  believes 
that  cancer  is  allied  to  the  group  of  specific  microbic  diseases, 
including  syphilis,  tuberculosis,  glanders,  leprosy,  and  actinomyco- 
sis.  He  claims  that  cancer  and  these  specific  infective  diseases  con- 
stitute a  group  of  growths  which  are  self- sustain  ing,  have  special 
modes  of  degeneration  and  of  ulceratiou,  to  which  they  all  tend ; 
are  all,  at  some  time,  either  infective  to  tissues  at  a  distance  by 
transportation  of  parts  of  the  growth  through  lymphatics  or  blood- 
vessels, or  to  adjacent  parts  by  invasion,  or  to  other  beings  by  inoc- 
ulation ;  and  finally  they  all  occur  by  preference  in  tissues  or  organs 
the  subject  of  local  injury  or  irritation.  He  is  strongly  inclined  to 
the  supposition  that,  like  in  the  infective  inflammatory  affections, 
the  cause  of  cancer  is  owing  to  the  presence  of  a  specific  microbe. 
As  the  essential  predisposing  cause  for  the  localization  of  the  as 
yet  unknown  cancer  microbe  he  regards  the  existence  of  a  suscepti- 
bility in  some  part  of  the  organism  which  determines  localization 
in  the  same  manner  as  is  furnished  by  the  brain  in  hydrophobia 
and  spinal  cord  in  tetanus. 

Microorganisms  have  been  found  in  the  tissues  of  superficial  car- 
cinoma and  in  secondary  carcinoma  of  internal  organs,  but  even 
Afauasieff,  who  studied  this  subject  with  the  greatest  care  in  Klebs's 
laboratory,  at  Prague  many  years  ago,  was  unable  to  find  them  in 
the  minute  miliary  nodules  of  disseminated  carcinoma.  Weigert 


250  ALLEGED     MICROBIC    ORIGIN    OF    TUMORS. 

found  bacilli  which  behaved  on  staining  like  tubercle  bacilli  in 
rapidly  growing  lympho-sarcoma,  and  Klebs  in  leukaemic  lympho- 
mata. 

In  the  fall  of  1 887,  Scheuerlen  (Deutsche  med.  Wochenschrift,  1887, 
No.  48)  read  a  paper  before  the  Medical  Society  at  Berlin  which  at  the 
time  attracted  a  great  deal  of  attention,  and  which  was  immediately 
noticed  by  every  medical  journal  on  both  continents.  In  this  paper 
he  put  forth  the  claim  that  he  had  discovered  the  microbe  of  carci- 
noma. From  ten  cases  of  carcinoma  of  the  breast  he  had  made 
inoculations  upon  solid  sterilized  ascites  and  hydrocele  fluid.  Usu- 
ally on  the  third  day  a  growth,  in  the  form  of  a  colorless  film,  was 
seen  on  the  surface  of  the  serum,  which  later  changed  into  a  yellow- 
ish-brown color.  On  microscopic  examination  it  was  found  that 
this  culture  was  composed  of  short  bacilli,  with  spores  which  could 
be  readily  stained  with  the  ordinary  reagents.  These  bacilli  could 
not  be  seen  in  stained  sections,  but  could  be  demonstrated  in  fresh 
cancer  juice.  Six  bitches  were  inoculated  by  injecting  material 
from  the  pure  cultures  directly  into  the  posterior  breast  gland,  and 
fourteen  days  later  a  circumscribed  tumor  the  size  of  a  walnut  had 
formed  at  the  point  of  inoculation.  In  the  animals  killed  four 
weeks  after  inoculation  the  tumors  examined  under  the  microscope 
were  seen  to  be  composed  of  epithelial  cells,  in  which  the  spores  of 
the  bacilli  could  be  readily  identified. 

In  the  discussion  which  followed  the  reading  of  this  paper,  Gutt- 
mauu  agreed  with  the  author  that  the  bacilli  were  the  cause  of  can- 
cer. Frankel  thought  that  the  microbes  entered  the  tumor  and 
their  presence  only  indicated  that  the  tumor  tissue  had  determined 
localization  of  floating  microbes.  In  the  same  journal  Schill,  of 
Dresden,  states  that  he  has  found  in  cancerous  and  sarcomatous 
tissues  rod-shaped  microbes  which  he  succeeded  in  cultivating  on 
gelatine. 

Freire  claims  priority  in  the  discovery  of  the  microbe  of  carci- 
noma. Perrin  and  Barnahei  and  Sanarelli,  both  of  Siena,  have 
also  found  a  bacillus  in  connection  with  the  etiology  of  malignant 
growths. 

Ballance  and  Shattock  (British  Med.  Journal,  Oct.  29,  1887) 
made  cultivations  from  twenty-two  cases  of  carcinoma,  the  majority 
of  which  only  yielded  negative  results.  When  a  growth  did  occur 
the  organisms  were  the  same  as  those  described  and  figured  by 
various  observers  as  occurring  in  healthy  tissues. 

Francke's  ("  Ueber  Aetiologie  und  Diagnose  von  Sarkom  und 
Carcinom,"  Munch,  med.  Wochenschrift,  1887)  experiments  began 
in  November,  1887,  and  he  had  already  seen  and  demonstrated  the 
bacillus  of  sarcoma  when  Scheuerlen's  discovery  was  announced. 
Francke  has  examined  nine  cancers  since  then,  and  in  all  has 


ALLEGED     MICKOBIC     OKIGIN    OF    TUMORS.  251 

observed  the  carcinoma  bacillus  and  its  spores  as  described  by 
Scheuerleu.  His  observations  on  the  bacillus  of  sarcoma  were 
based  on  the  examination  of  three  cases. 

The  bacillus  found  in  them  was  thinner  and  longer  than  the  can- 
cer-bacillus. The  cancer-bacillus,  on  the  average,  is  2  micromilli- 
metres  long,  and  0.4  micromillimetre  broad,  while  the  sarcoma 
bacillus  measures  3  to  4  by  0.4  micromillimetres.  The  spores  of 
the  sarcoma  bacillus  also  resemble  the  spores  of  the  cancer-bacillus, 
except  that  they  are  a  little  larger  and  have  a  sharply-contoured 
pole.  The  two  microbes  were  cultivated  upon  the  same  nutrient 
soil,  producing  a  brown  pigment.  Inoculations  of  the  pure  culture 
of  the  sarcoma  bacillus  have  produced  no  results  as  yet,  but  Francke 
thinks  that  four  weeks  is  too  short  a  time  for  sarcoma  to  develop, 
and  he  will  make  another  report  later.  Pfeiifer  ("  Der  Scheuer- 
len'scheKrebs-bacillusein  Saprophyt,"  Deutsche  med.  Wochenschrift, 
1888,  No.  11)  holds  that  Scheuerlen's  carcinoma  bacillus  is  a  sapro- 
phyte and  identical  with  the  proteus  mirabilis  of  Hauser. 

Baumgarten  ("  Ueber  Scheuerlen's  Carcinom-bacillus,"  Oentral- 
blatt  f.  Baderiologie  u.  Parasitenkunde,  B.  iii.,  No.  13)  found  a 
potato  bacillus  which  in  size  and  shape  resembled  Scheuerlen's 
bacillus  of  cancer,  only  that  it  exerted  a  somewhat  liquefying  effect 
on  gelatine.  He  found  a  similar  bacillus  in  a  sarcoma  of  the  skull 
and  breast  and  in  a  neuroma  of  the  hand.  That  Scheuerlen's 
bacillus  has  no  direct  etiological  bearing  to  cancer,  he  claims  is 
proved  both  by  its  occurrence  in  other  tumors,  and  that  it  is  not 
always  present  in  carcinoma.  He  believes  that  it  is  a  potato  bacil- 
lus which  has  a  wide  distribution  and  consequently  likely  to  con- 
taminate culture  media. 

Senger  ("  Studien  zur  Aetiologie  des  Carciuoms,"  Berl.  Jclin. 
Wochenschrift,  1888),  in  comparing  malignant  tumors  with  infec- 
tive processes,  affirms  that  their  resemblance  is  marked.  Thus 
carcinoma,  like  a  phlegmonous  inflammation,  follows  the  lymphatic 
system,  and,  as  in  pyaemia,  gives  rise  to  metastasis.  Again,  in  rare 
cases,  carcinoma  appears  as  a  miliary  affection,  which  in  a  very 
short  time  becomes  diffuse  and  leads  to  serious  disturbances  of  the 
digestive  and  circulatory  organs.  Such  cases  can  only  be  explained 
by  assuming  that  minute  infective  particles  are  introduced  into  the 
circulation  which  give  rise  to  innumerable  embolic  obstructions  in 
the  capillary  vessels  where  independent  centres  of  growth  are  estab- 
lished. As  a  last  resemblance  may  be  mentioned  those  numerous 
cases  of  tar,  paraffin,  and  chimney-sweeper's  cancer,  which  often 
attack  young  persons  in  whom  no  predisposition  to  cancer  exists. 
Senger  does  not  believe  that  the  cause  of  cancer  is  a  microbe. 
Under  strict  antiseptic  precautions  he  made  implantation  experi- 
ments of  carcinoma  tissue  in  mice,  rabbits,  and  dogs,  and  on  exam- 


252  ALLEGED     MICEOBIC    OKIGIN    OF    TUMOKS. 

ining  the  site  of  implantation  at  different  times  noticed  that  the 
malignant  graft  was  in  process  of  absorption,  or  had  disappeared 
completely,  leaving  only  a  minute  cicatrix  at  the  point  where  it  had 
been  embedded.  The  experiments  yielded  no  better  results  if  the 
animals  were  subjected  to  starvation  before  inoculation,  or  if  their 
health  was  impaired  from  any  other  cause. 

Thoma  (Fortschritte  der  Medecin,  June  1, 1889)  has  found  in  the 
muscles  of  carcinoma  of  rectum,  stomach,  and  mamma,  small,  uni- 
cellular protoplasmic  cells,  refracting  light  strongly,  with  nucleus 
and  sometimes  a  nucleolus  also,  which  stain  with  hsematoxyliu, 
eosin,  saffron,  and  alum  carmine,  which  he  considers  undoubtedly 
parasitic.  In  shape  they  are  irregularly  rounded,  or,  more  com- 
monly, oval ;  occur  singly  or  in  groups  of  from  four  to  six  in  an 
epithelial  nucleus  which  appears  as  a  hollow  bladder  with  granular 
portions  besides  the  parasites.  In  birds  epithelial  tumors  are  pro- 
duced by  similar  bodies,  hence  inference  that  they  are  the  cause. 
This  is  questionable,  because  Steiuhaus  and  Heidenhain  have  found 
similar  organisms  in  the  epithelial  lining  of  the  salamander's  bowel 
without  any  pathological  significance. 

At  the  meeting  of  the  German  Congress  of  Surgeons  in  1888, 
Hahu  ("  Ueber  Transplantation  von  carcinomatoser  Haut,"  Berl.  Min. 
Wochenschrift,  May  4,  1888)  gave  an  account  of  a  successful  experi- 
ment which  he  had  made  on  a  woman  suffering  from  a  recurring 
carcinoma  of  the  breast  which  had  advanced  beyond  the  reach  of 
operative  treatment.  The  breast  had  been  previously  extirpated 
and  she  was  now  suffering  from  an  extensive  local  recurrence  with 
innumerable  nodules  in  the  skin.  He  removed  six  small  nodules 
with  the  entire  thickness  of  the  skin,  and  then  planted  them  upon 
the  opposite  healthy  breast,  from  which  six  similar  pieces  of  skin 
had  been  removed.  The  healthy  skin  was  grafted  upon  the  places 
where  the  nodules  had  been  excised.  The  dressing  was  not 
changed  until  the  thirteenth  clay,  when  all  the  malignant  grafts 
were  found  adherent  and  slightly  elevated  above  the  niveau  of  the 
surrounding  skin.  Four  weeks  after  the  grafting  minute  nodules 
were  found  around  two  of  the  grafts.  All  the  grafts  continued  to 
increase  in  size,  and  at  the  time  of  death  (ten  weeks)  had  attained 
the  size  of  cherry-stones.  Microscopical  examination  of  the  nodules 
surrounding  three  of  the  grafts  revealed  the  histological  structure 
of  true  carcinoma.  He  believed  that  the  success  which  attended 
his  experiment  was  due  to  the  fact  that  only  new  cells  were  taken 
by  the  excision  and  implantation  of  recent  nodules.  In  referring 
to  the  literature  on  the  subject  of  cancer  inoculations,  he  states  that 
the  first  successful  inoculation  was  made  by  Langenbeck,  who  in- 
jected cancer  juice  into  the  jugular  vein  of  a  dog,  and  two  months 
later  it  was  claimed  that  two  cancerous  nodules  were  found  in  the 


ALLEGED    MICROBIC     ORIGIN    OF    TUMORS.  253 

lung.  Foil  in  and  Lebert  asserted  that  they  had  been  similarly 
successful  in  transmitting  the  disease  from  man  to  animals.  From 
sixty  to  seventy  grammes  of  finely  triturated  cancer  juice  taken 
from  a  cancer  of  the  breast  were  mixed  with  distilled  water  and 
injected  into  the  jugular  vein  of  a  dog.  The  animal  died  two 
weeks  after  the  inoculation,  when  a  few  firm  elastic  nodules,  the 
size  of  a  pea,  were  found  in  the  walls  of  the  heart,  and  numerous 
nodules,  the  size  of  the  head  of  a  pin,  throughout  the  liver.  Bill- 
roth,  Maas,  Doutrelepont,  Alberts,  Senger,  and  others  obtained 
only  negative  results.  Doutrelepont  made  inoculations  from  ani- 
mal to  animal  with  no  better  effect.  In  cases  of  cancer  of  the  peri- 
toneum it  has  been  known  for  a  long  time  that  local  dissemination 
takes  place  by  detached  minute  particles  leaving  the  primary  matrix 
and  becoming  implanted  upon  the  peritoneal  surface  forming  new 
independent  centres  of  growth.  Implantation  of  cancer  cells  upon 
the  surface  of  wounds  made  for  the  removal  of  a  carcinoma  has  been 
recognized  as  one  of  the  ways  in  which  the  disease  returns.  Trau- 
matic dissemination  of  carcinoma  is  recognized  by  Billroth,  \Val- 
deyer,  Bergmanu,  Reineke,  and  others. 

At  a  meeting  of  the  Medical  Society  in  Zurich,  Hauau  (British 
Med.  Journal,  October  19,  1889)  claimed  that  he  had  succeeded  in 
inoculating  carcinoma  from  rat  to  rat.  On  November  28,  1888, 
he  excised  two  pieces  of  a  carcinomatous  lymphatic  gland  from  a 
female  rat  with  malignant  disease  of  the  vulva,  and  transplanted 
these  into  the  right  half  of  the  scrotum  in  two  male  rats.  One  of 
the  latter  died  on  January  14,  1889.  The  necropsy  revealed  a 
generalized  carcinosis  of  the  peritoneum  and  omentum.  In  the 
other,  which  was  killed  on  January  25th,  there  were  found  two 
typical  cancroid  nodules,  the  size  of  a  pea,  on  the  gubernaculum 
testis  and  the  cauda  of  the  epididymis.  The  transplanted  malig- 
nant growths  proved  to  have  precisely  the  same  structure  as  those 
which  had  spontaneously  originated  in  the  first  animal.  According 
to  Hanau's  theory,  the  carciuomatous  infection  should  be  attributed 
to  the  agency  of  young  epithelial  cells  and  not  to  any  pathogenic 
microbe.  This  theory  would  explain  satisfactorily  the  few  instances 
where  transplantation  of  malignant  grafts  yielded  a  positive  result. 

During  the  last  eight  years  I  have  made  numerous  implantation 
experiments  of  carcinoma  and  sarcoma  tissue  in  dogs,  cats,  rabbits, 
and  guinea-pigs,  and  have  invariably  observed  that  the  graft  failed 
to  increase  in  size.  The  apparent  increase  in  size  a  few  days  after 
implantation  was  due  to  the  formation  of  a  wall  of  granulation 
tissue  around  the  graft  in  which  it  becomes  embedded.  The  ex- 
periments were  made  by  taking  a  graft  the  size  of  a  pea  from  the 
periphery  of  the  malignant  tumor  and  inserting  it  under  the  skin, 
usually  in  the  inguinal  region.  After  three  to  four  weeks  without 


254:  ALLEGED     MICKOBIC    OEIGIN    OF    TUMOKS. 

exception  the  graft  was  found  absorbed  and  its  place  occupied  by  a 
subcutaneous  cicatrix.  At  least  twenty- four  such  experiments  were 
made  with  the  same  uniform  negative  results.  The  comparative 
rarity  of  malignant  tumors  in  animals  made  it  difficult  for  me  to 
carry  out  the  plan  of  inoculating  from  animal  to  animal.  I  finally 
came  in  possession  of  a  dog  which  had  a  sarcoma  of  the  lower  jaw. 
Implantation  experiments  were  made  on  the  same  animal  and  a 
number  of  other  dogs,  but  in  all  of  them  the  grafts  were  absorbed 
as  promptly  as  when  tumor  tissue  from  the  human  subject  was 
used.  I  finally  decided  on  making  an  implantation  experiment  on 
man  in  the  first  case  in  which  such  an  experiment  would  be  justi- 
fiable from  the  hopelessness  of  the  case.  The  case  that  I  selected 
was  a  large  carcinoma  of  the  leg  which  had  taken  its  origin  from 
the  skin  and  in  which  amputation  was  objected  to.  The  fungous 
surface  was  scraped  and  cauterized  and  from  the  deepest  portion  of 
the  growth  a  piece  of  tissue,  the  size  of  a  peach-stone,  was  inserted 
through  a  small  incision  into  the  connective  tissue  over  the  poste- 
rior aspect  of  the  leg  and  the  wound  sutured  with  fine  catgut. 
Primary  union  took  place,  with  circumscribed  infiltration  of  tissue 
around  the  graft  from  the  second  day  to  the  end  of  the  first  week, 
After  this  time  gradual  disappearance  of  the  graft  by  absorption 
occurred,  until,  at  the  end  of  four  weeks,  it  had  entirely  disappeared. 
At  the  meeting  of  the  German  Congress  of  Surgeons  in  1889,  Wehr 
("Weitere  Mittheilungen  iiber  diepositiven  Ergebuisseder  Carcinom- 
ueberimpfungeu  von  Huud  auf  Hund")  admitted  that  in  the  animals 
which  he  showed  at  the  previous  meeting  the  nodules  had  since  be- 
come smaller  and  smaller  and  finally  disappeared  completely  ;  but 
he  made  the  statement  that  since  that  time  he  had  not  only  been 
able  to  inoculate  a  dog  successfully  by  implantation  of  carcinomatous 
tissue,  but  that,  in  one  instance  at  least,  the  animal  died  of  carci- 
noma. His  transplantations  were  made  from  animal  to  animal. 
He  infected  twenty-six  dogs,  using  tissue  from  five  bitches  affected 
with  vaginal  carcinoma  and  two  dogs  suffering  from  carcinoma  of 
the  penis.  Under  strict  antiseptic  precautions  a  small  incision  was 
made  in  the  skin,  and  then  a  trocar  was  inserted  to  the  depth  of 
three  or  four  cm.,  and  through  the  canula  the  fragment  of  cancer 
tissue  was  deeply  embedded.  Six  of  the  animals  had  to  be  killed 
three  and  four  weeks  after  the  inoculation,  because  they  had  been 
bitten  by  a  dog  which  was  supposed  to  have  hydrophobia.  In  the 
remaining  animals  he  obtained  twenty-four  nodules,  five  of  which 
were  examined  at  a  time  when  possibly  they  might  have  continued 
to  increase  in  size,  while  the  remaining  nodules  were  all  absorbed. 
In  a  bitch  which  was  inoculated  December  12,  1887,  in  four  places 
in  the  region  of  the  mammary  gland,  the  nodules  increased  in  size 
until  they  were  as  large  as  a  plum  or  hazelnut.  In  April  of  the 


ALLEGED    MICROBIC     ORIGIN    OF    TUMORS.  255 

following  year  the  tissues  around  the  tumors  became  the  seat  of 
inflammation,  which,  however,  soon  subsided.  The  tumors  in- 
creased in  size,  and  the  following  June  the  animal  lost  flesh  rapidly 
and  died  the  middle  of  the  same  mouth.  The  autopsy  showed 
metastatic  tumors  in  the  pelvis  and  along  the  lumbar  portion  of 
the  spine.  The  tumor  in  the  pelvis  had  compresed  the  urethra  so 
firmly  that  the  bladder  ruptured — an  accident  which  was  the  direct 
cause  of  death.  Two  carcinomatous  nodules  were  also  found  in  the 
chest.  Makra  has  been  making  a  series  of  bacteriological  studies 
on  malignant  tumors  in  the  laboratory  of  Kovacs,  but,  so  far,  only 
negative  evidence  has  been  obtained. 

Galippe  and  Landouzy  ("  Note  sur  la  presence  de  parasites :  1, 
dans  les  tumeurs  fibreuses  (myomes)  uterines ;  2,  dans  le  liquide 
des  kystes  ovariens  et  sur  leur  role  pathogenique  probable,"  Graz. 
des  Hop.,  1887,  No.  24)  have  extended  the  bacteriological  investi- 
gations of  the  microbic  origin  of  tumors  to  the  benign  variety.  In 
two  cases  of  extirpation  of  myomatous  tumors  of  the  uterus  they 
inoculated  a  nutrient  medium  with  the  tumor  tissue,  and  three  days 
later  found  numerous  microorganisms ;  the  most  conspicuous  was 
a  diplococcus  arranged  in  groups,  or  in  long  chains ;  also  strepto- 
cocci and  bacilli.  The  same  microbes  were  found  in  both  tumors. 
The  same  authors  also  found  microorganisms  in  the  contents  of  two 
ovarian  cysts.  They  believe  that  solid  and  cystic  tumors  develop 
in  consequence  of  the  entrance  of  microbes  into  the  organism  in  the 
same  manner  as  parasites  cause  excrescences  in  plants. 

In  1888  Neisser  (  Vierteljahrsschr if tfiirl)ermatologieund  Syphilis, 
1888)  published  an  elaborate  paper  on  the  microbic  origin  of  tumors 
containing  the  results  of  his  own  observations,  in  which  he  places 
the  parasite  in  the  coccidia  groups  of  the  sporozoa. 

The  following  year  Darier  (Archiv  de  Med.  Experimental^  et 
d*  Anatomic  Pathologique,  March  1,  1890)  made  two  reports  of  the 
result  of  his  work  in  Malassez's  laboratory.  In  the  first  of  these 
he  intimated  the  recognition  of  a  coccidium  in  a  case  of  acne  eornee, 
and  defines  the  condition  as  a  psorospermose  cutanee ;  in  the  second 
he  announced  that  he  had  found  a  parasite  belonging  to  the  same 
class  in  a  case  of  Paget's  disease  of  the  nipple.  He  claims  that  this 
parasite  presents  all  the  different  morphological  phases  of  develop- 
ment characteristic  of  this  organism ;  at  first  a  naked  mass  of  pro- 
toplasm, afterward  surrounded  by  an  envelope,  then  the  protoplasm 
dividing  into  numerous  granules,  which  being  surrounded  by  the 
cell-membrane,  presents  the  appearance  of  a  cyst.  He  regards  the 
disease  in  which  these  formations  are  formed  as  parasitic,  a  psoro-* 
spermose.  The  same  year  Albarran  ( La  Scmaine  Medicale,  1889, 
p.  101)  informed  the  society  that  he  had  found  a  similar  parasite  in 
two  epithelial  tumors  of  the  jaw. 


256          ALLEGED    MICROBIC    ORIG-IX    OF    TUMORS. 

About  the  same  time  Thoma  (Fortsehritte  der  Medicin,  June  1, 
1889)  published  a  short  paper  on  "A  Characteristic  Parasitic 
Organism  in  the  Cells  of  Carcinoma."  He  describes  the  parasite 
which  he  found  in  malignant  growths  as  a  unicellular  organism, 
consisting  of  protoplasm  and  a  nucleus,  with  sometimes  a  uucleolus. 
In  shape  it  is  round  or  oval,  and  he  found  it  most  frequently  in  the 
vacuolated  nucleus,  in  other  cases  near  the  nucleus. 

In  January,  1890,  Wickham  (Archives  de  Medecine  Experi- 
mentale  et  d'Anatomie  Pathologique,  1890,  p.  46)  published  an 
exhaustive  paper  on  "  The  Pathological  Anatomy  and  the  Nature 
of  Paget's  Disease  of  the  Nipple/7  in  which  he  describes  and  figures 
a  parasite  which  he  regards  as  coccidia  or  psorospermise. 

This  parasite  consists  of  a  double-contoured  capsule  either  filled 
with  protoplasm,  or  the  protoplasm  is  gathered  into  a  mass  in  the 
centre.  As  the  sporozoa  reproduce  themselves  by  the  formation  of 
spores,  the  author  does  not  appear  to  have  observed  this  process  in 
connection  with  the  organism  which  he  described. 

During  the  last  year  Klebs  (Deutsche  med.  Wochenschrift,  Nos. 
24,  25,  28, 1890)  published  a  series  of  papers  on  "The  Nature  and 
Diagnosis  of  Cancer-formation,"  in  which  he  discusses,  with  his 
usual  ability  and  thoroughness,  the  microbic  origin  of  carcinoma. 
He  describes  hyaline  bodies  in  carcinoma  tissue,  which,  however,  he 
regards  as  products  of  degenerative  changes.  He  met  with  these 
bodies,  presenting  either  an  angular  or  rounded  form  in  the  prolifer- 
ating epithelial  tubes,  and  also,  but  less  numerously,  in  the  stroma, 

Sjobring  (Fortsehritte  der  Medicin,  No.  14,  1890)  describes  a 
"  Parasitic  Protozoa-like  Organism  in  Carcinoma/'  which  he  found 
in  six  cases  of  mammary  carcinoma. 

The  most  recent  publication  on  this  subject  is  from  the  pen  of 
William  Russel,  of  Edinburgh  ("An  Address  on  a  Characteristic 
Organism  of  Cancer,"  British  Medical  Journal,  December  13, 1890). 
He  has  found  in  carcinoma  tissue  and  a  few  other  pathological  pro- 
ducts certain  bodies,  which  for  want  of  reliable  knowledge  concern- 
ing their  nature  and  on  account  of  their  specific  reaction  to  certain 
staining  materials,  he  calls  "  fuchsine  bodies."  The  following  are 
his  directions  for  staining  :  "  1.  Saturated  solution  of  fuchsine  in  2 
per  cent,  carbolic  acid  in  water.  2.  1  per  cent,  solution  of  iodine- 
green  (Griiber's),  in  2  per  cent,  carbolic  acid  in  water.  Place  sec- 
tion in  water ;  then  stain  in  fuchsine  ten  minutes  or  longer ;  wash 
for  a  few  minutes  in  water;  then  wash  for  half  a  minute  in  absolute 
alcohol.  From  this  put  the  section  into  the  solution  of  iodine- 
•green,  and  allow  it  to  remain  well  spread  out  for  five  minutes.  From 
this  rapidly  dehydrate  in  absolute  alcohol,  pass  through  oil  of  cloves 
and  mount  in  balsam.  Tissues  stained  by  this  process  containing 
the  "  fuchsine  bodies"  presented  a  characteristic  and  striking  ap- 


ALLEGED     MICKOBIC    ORIGIN    OF    TUMORS.  257. 


FIG.  9. 


A,  mass  of  fungi :  B,  individual  giving  off  bud;  C, -same,  with  bud  further  removed 
from  parent  but  still  attached;  D,  four  individuals  attached  to  one  another;  F, small 
spores  in  lymph  cells  and  leucocyte;  G,  altered  leucocyte  containing  spore. 

17 


258          ALLEGED     MICKOBIC    ORIGIN    OF    TUMORS. 

pearance  when  examined  under  high  power  and  with  the  assistance 
of  Abbe's  sub-stage  condenser.  The  brilliant  red  or  purplish-red 
color  of  the  "  fuchsine  bodies"  forms  a  striking  contrast  to  the 
green  and  delicate  purple  of  the  tissues.  He  found  these  bodies 
grouped  in  the  interior  of  cells,  usually  surrounded  by  a  vacuole. 

Their  intra-cellular  location  and  manner  of  reproduction  is  well 
shown  by  the  accompanying  illustration  (Fig.  9).  He  found  these 
bodies  invariably  present  in  forty-five  specimens  of  carcinoma  taken 
from  so  many  different  individuals.  He  regards  the  organism 
described  as  a  species  of  fungus  which  belongs  to  the  sprouting 
fungi  (Sprosspilze  of  Nageli),  and  believes  that  a  direct  etiological 
relationship  exists  between  it  and  the  development  of  a  carcinoma. 

At  a  meeting  of  the  Royal  Academy  of  Medicine  in  Ireland, 
Patterson  (British,  Medical  Journal,  December  6, 1890)  read  a  paper 
on  psorospermosis  and  its  relation  to  cutaneous  carcinoma  in  the 
light  of  recent  researches,  illustrated  by  drawings  aud  microscopic 
specimens  exhibiting  coccidia  in  proliferating  epithelium.  In  the 
discussion  McKee,  while  admitting  that  coccidia  might  ultimately 
be  shown  to  be  the  cause,  or  at  least  one  cause,  of  cutaneous  and 
perhaps  other  forms  of  carcinoma,  led  to  the  inference  that  the  im- 
perfect knowledge  available  at  present  rather  pointed  against  than 
in  favor  of  this  view.  He  maintained  that  Paget's  disease  of  the 
nipple  resembled  eczema,  and  was  apparently  inflammatory,  yet  the 
same  form  of  coccidium  found  in  it  was  also  credited  with  the  pro- 
duction of  the  malignant  tumor  of  the  breast  which  sometimes  fol- 
lowed it.  He  thought  it  more  probable  that  Paget's  disease  simply 
acted  as  one  of  many  irritants,  any  one  of  which  might  give  rise 
to  a  malignant  tumor  in  a  part  already  predisposed  to  it. 

The  strongest  proof  against  the  microbic  nature  of  carcinoma 
is  the  histological  structure  of  all  products  of  infective  processes. 
The  products  of  all  diseases,  so  far  as  known,  which  are  caused  by 
microbes  and  are  characterized  by  local  inflammatory  processes, 
consist  primarily  of  granulation  tissue.  The  new  tissue  surround- 
ing the  seat  of  infection  is  a  homoplastic  product  which  originates 
from  preexisting  tissues.  So  far,  we  have  no  knowledge  of  a 
microbe  which  produces  heteroplastic  tissue  proliferation ;  that  is, 
the  production  of  cells  which  do  not  preexist  in  that  locality. 
Many  of  the  lymphomata  undoubtedly  owe  their  origin  to  specific 
microbes,  but  these  are  not  true  tumors,  and  should  be  classified 
with  the  inflammatory  infective  swellings — the  granulomata. 

There  has  been,  so  far,  no  proof  furnished  of  the  existence  of  a 
specific  bacillus  in  carcinoma  or  sarcoma,  and  the  inoculation  and 
implantation  experiments  have  proved  so  seldom  successful,  and 
the  experiments  which  at  first  appeared  successful,  have  later 


ALLEGED     MICROBIC    ORIGIN    OF    TUMORS.  259 

been  shown  to  be  so  deceptive,  that  the  microbic  origin  of  malignant 
tumors  has  not  only  not  been  established,  but  rendered  improbable. 
The  analogy  between  tumors  and  infective  processes  is  more  appa- 
rent than  real,  and  simply  consists  in  the  fact  that  the  cells  of  the 
former  endowed  with  all  the  properties  of  independent  growth 
select  the  same  routes  for  local  and  general  dissemination  as  the 
microbes  of  the  latter. 


INDEX  OF  SUBJECTS. 


A  BSCESS,  description  of  minute,  88 
•AA     gonococci  in,  236 

tubercular,  197 
Actinomycosis  hominis,  213 

clinical  history  of,  218 
fungus  of,  cultivation  of,  215 
description  of,  214 
effect  of,  on  the  tissues,  217 
inoculation  experiment  with,  216 
staining  of,  214 

infection  through  the  skin,  220 
.through  carious  teeth,  221 
of  brain,  228 
of  intestines,  224 
of  jaw,  221 
of  lung,  227 
of  skin,  220 

sources  of  infection,  217 
Antagonism  among  microorganisms,  68 
Anthrax,  199 

attenuation  of  virus  of,  201 

bacillus   of,   antagonistic  to  pneumo- 

coccus  of  Friedlander,  68 
cultivation  of,  200 
description  of,  200 
localization  of,  39 
staining  of,  200 
cause  of  death  in,  204 
direct  transmission  of,  21 
in  man,  202 
inoculation  of,  201 
intensification  of  virus  of,  202 
prophylaxis  by  streptococcus  of  erysip- 
elas, 68 

relation  of,  to  trauma,  38 
Arthritis,  gonorrhoeal,  237 
purulent,  100 


BACILLUS  ANTHRACIS,  200 
cultivation  and  staining  of,  200 
coli  communis,  77 


Bacillus  mallei,  208 

staining  of,  208 
of  glanders,  208 
of  smegma,  246 
of  syphilis,  241 
peritonitidus   ex-intestinalis  cuniculi, 

76 

pyocyaneus,  84 
pyogenes  foetidus,  84 
saprogenes,  106 
tetani,  143 

tuberculosis,  cultivation  of,  158 
description  of,  157 
in  milk,  66 
inoculation    experiments   with, 

159 

its  discovery,  156 
staining  of,  158 
Bacteria,  ectogenous,  29 

endogenous,  29 
Bones,  tuberculosis  of,  181 

always  secondary,  181 
changes  in,  182 


,  89 
Cancer,   peritoneal   dissemination   of, 

253 

supposed  bacillus  of,  250 
transplantation  experiments  with, 

252 

traumatic  dissemination  of,  253 
Chemical  irritants  as  a  cause  of  suppura- 
tion, 92 
Circulation,  force  of,  in  relation  to  microbic 

disease,  28 

Circumcision,  tuberculosis  following,  168 
Cladothrix,  140 
Coccidia,  256 

Coli  communis,  bacillus  of,  77 
Corpora  oryzoidea,  188 


262 


INDEX    OF    SUBJECTS. 


TjICZEMA,  tubercle  bacilli  in,  175 
-L^    Elimination   of  pathogenic   microor- 
ganisms, 56 
by  leucocytes,  56 

in  pyaemia,  128 
Embolism  in  pyaemia,  128 

in  tuberculosis,  161 
Empyema,  98 

Epididymis,  tuberculosis  of,  193 
Erysipelas,  129 

cause  of  death  in,  136 

direct  transmission  of,  20 

history  of,  129 

manner  of  infection  in,  133 

microbe  of,  130 

relation  of,  to  puerperal  fever,  133 

to  phlegmonous  inflammation  and 

suppuration,  135 

streptococcus  of,  antagonistic  to  syph- 
ilis, 69 

preventive    and    curative  of  an- 
thrax in  animals,  69 
therapeutic  inoculation  of,  131 
Erysipeloid,  139 


TjVRIEDLANDER,  pneumococcus  of, 
-T      Fuchsine  bodies,  256 


p  ANGLION,  compound,  1 87 
\J     Gangrene,  106 

microbes  the  cause  of,  106 
with  emphysema,  107 
Genital  organs,  tuberculosis  of,  192 
Giant  cells  (phagocytosis),  56 
Glanders,  207 

bacillus  of,  208 

cultivation  and  staining  of,  208 
in  man,  211 

inoculation  experiments,  209 
not  transmissible  by  air,  35 
Gonococcus  of  Neisser,  231 

action  of,  on  peritoneum,  234 

on  other  tissues,  234 
cultivation  of,  230 
description  of,  230 
diagnostic  value  of,  230 
in  abscess,  236 

inoculation  experiments  with,  233 
in  purulent  ophthalmia,  236 


Gonococcus,  staining  of,  231 
Gonorrhoea,  2  30 
Gonorrhoeal  rheumatism,  237 
Granulation  tissue  in  infective  inflamma- 
tion, 73 
in  simple  inflammation,  71 


HEALTH,  state  of,  in  relation  to  microbic 
disease,  28 
Hereditary  predisposition,  19 

transmission  of  microbic  disease,  19 
clinical  evidences  of,  20 
experimental     evidences 

of,  22 
Hygroma,  188 


INFECTION  by  inhalation,  32 

1     mixed,  48 
sources  of,  29 

Inflammation,  71 

phlegmonous  and  erysipelatous,  135 
relation  to  metastatic  suppuration,  51 
simple  and  infective,  71,  72 


"OINTS,  tuberculosis  of,  184 


17RYPTO-GENETIC  septico-pysemia,  122 


1"  EUCOCYTES  as  eliminators  of  micro- 
1^    organisms,  57 
Leucomaines,  111 
Lupus,  170 

bacillus  of  tuberculosis  in,  173 
identical  with  tuberculosis,  171 
inoculation  with,  produces  tuberculosis, 

159 
Lymphatic  glands,  tuberculosis  of,  175 

spontaneous  cure  by  suppura- 
tion, 178 
treatment  of,  181 
Lymphomata,  microbic  origin  of,  258 


MACROPHAGI,  60 
Malaria  infections,  urine  of,  65 
Malignant  oedema,  114 


INDEX    OF    SUBJECTS. 


263 


Malignant  oedema,  direct  transmission  of, 

23 

Malleus  humidus,  207 
Mamma,  tuberculosis  of,  194 
Mastitis,  suppurative,  72 
Metastatic  suppuration,  51 
Miasma,  29 
Microbes,  cause  of  infective  inflammation, 

72 

encapsulation  of,  53 
localization    of,   in    pathological    pro- 
ducts, 47 

Microbic  disease  in  relation  to  force  of  cir- 
culation, 28 
to  state  of  health,  28 
origin  of  cancer,  249 

of  lymphomata,  258 
of  myoma,  255 
of  ovarian  cysts,  255 
Micrococci  in  urine,  115 
Micrococcus  pyogenes  tenuis,  82 
Microorganisms,  antagonism  among,  68 
excreted  in  urine,  64 
pathogenic,  elimination  of,  56 
by  phagocytosis,  56 
by  kidney  and  other  organs, 

63 
in  atmospheric  air,  31 

detection  and  estimation 

of,  32 

in  healthy  body,  26 
in  hospital  wards,  34 
localization  of,  37 

in  relation  to  trauma,  37 
removed  by  red  blood-corpuscles, 

26 

thermal  death-point  of,  29 
Microphagi,  60 
Mikrosporoii  septicum,  110 
Milk,  bacillus  of  tuberculosis  in,  66 

in  puerperal  disease,  66 
Mixed  infection,  48 
Mouth,  tuberculosis  of,  191 
Mycosis,  121 

toxic,  of  the  blood,  122 


NAGELI,  Sprosspilze  of,  258 
Noma,  141 


/T?DEMA,  malignant,  114 
VJU     Ophthalmia,  purulent,  236 
Osteomyelitis,  acute  suppurative,  100 

caused  by  intra-uterine  infection,  21 

chronic,  54 

tubercular,  182 


PATHOLOGY,  its  relation  to  bacteriology, 
17 
Peritoneum,  tolerance  of,  to  pus-microbes, 

78 

to  unfiltered  air,  77 
tuberculosis  of,  189 

treatment  of,  190 
Peritonitis,  97 

experimental,  73 
perforative,  75 
septic,  78 

following  inflammation  of  the  in- 
testinal wall,  71 
simple,  78 
Phagocytosis,  56,  60. 

Placenta,  its  relation  to  the  passage  of  mi- 
crobes, 20-23 
Pneumococcus  of  Friedlander  antagonistic 

to  bacillus  anthracis,  68 
Predisposition,  hereditary,  19 
Proteus  mirabilis,  119 
vulgaris,  119 
Zenkeri,  119 
Psorospermia,  256 

Ptomaine  of  bacillus  prodigiosus  prevents 
growth  of  pus-microbes  in  culture  me- 
dium, 70 
Ptomaines,  119 

diffusion  of,  prevented  by  leucocytes, 

58 

discovery  of,  117 
effect  of,  on  leucocytes,  90 
in  relation  to  suppuration,  89 
prevent  coagulation  of  blood,  91 
Puerperal  disease,  milk  in,  66 
Pus  microbes  the  cause  of  suppuration,  84 
classification  and  description  of,  81 
growth   of,   in    culture    medium, 
prevented  by  ptomaine   of  ba- 
cillus prodigiosus,  70 
localization  of,  43 
their  relation  to  pyaemia,  126 


264 


INDEX    OF    SUBJECTS. 


Pus  microbes,  tolerance  of  peritoneum  to, 

77 
Pyaemia,  124 

artificial,  124 

changes  in  vessel-wall  in,  127 

chronic,  128 

relation  of  pus  microbes  to,  126 

thrombosis  and  embolism  essential  to, 

128 
Pyocyanin,  84 


•RHEUMATISM,  gonorrhoeal,  237 
-K.    Eice  bodies,  188 


O  APILEMIA,  116,  122 

IJ    Schizomycetes,  113,  119 

Scrofula  identical  with  tuberculosis,  161 

Sepsin,  117 

Septicaemia,  110 

history  of,  110 

progressive,  in  man,  121 
Septic  intoxication   from    introduction   of 

putrid  substances,  116 
Septico-pysemia,  122 

Serous  cavities,  suppurative  affections  of,  97 
Skin,  actinomycosis  of,  infection  through, 
220 

suppurative  affections  of,  96 

tuberculosis  of,  170 
Smegma,  bacillus  of,  246 
Spasmatoxin,  151 
Staphylococci  in  suppurative  mastitis,  72 

in  urine,  67 
Staphylococcus  cereus  albus,  82 

cereus  flavus,  82 

flavescens,  82 

pyogenes  albus,  81,  85 

pyogenes  aureus,  81,  85 

action  of,  on  peritoneum,  74 

pyogenes  citreus,  82 
Streptococci  in  suppurative  mastitis,  72 
Streptococcus  erysipelatosus,  129 

antagonistic  to  syphilis,  69 
preventive  and  curative  of  anthrax 

in  animals,  69 
therapeutic  inoculation  with,  131 

pyogenes,  83,  85 
Suppuration,  79 

caused  by  pus  microbes,  84 


Suppuration,  chemical  irritants  not  a  cause 

of,  87,  88,  92 
in  relation  to  erysipelas,  135 

to  ptomaines,  89 
history  of  investigation  of,  79 
m  eta  static,  51 
Surgical  tuberculosis,  170 
Synovitis,    experimental,    by    inoculation 

with  scarlatina-diphtheria  cocci,  49 
multiple  suppurative,  following  scarlet 

fever,  48 
Syphilis,  241 

bacillus  of,  241 

cultivation  and  staining  of,  242 
effect  of  erysipelas  on,  69 
inoculation  experiments,  24,  243 
Syphilitic  lesions,  secondary  infection  with 

pus  microbes,  247 
favorable  soil  for  growth  of  bacillus 
of  tuberculosis,  49 


TENDO-VAGINITIS  granulosa,  187 
synovitis,  187 

Testicle,  tuberculosis  of,  195 
Tetanin,  151 
Tetanotoxin,  151 
Tetanus,  142 

bacillus  of,  143 

occurrence  of,  in  earth,  150 
chronic,  153 

incubation  period  of,  153,  154 
inoculation  experiments,  144 
ptomaines  of  bacillus  the  cause  of,  151 
Thrombosis  in  pyaemia,  128 

in  tuberculosis,  181 

Transmission  of  microbic  disease  heredi- 
tary, 20 

Trauma    favors    localization    of   pus    mi- 
crobes, 43 

bacillus  tuberculosis,  41 
Toxic  mycosis  of  blood,  122 
Toxin,  muriate  of,  151 
Trypsin    injected    into   peritoneal    cavity 

causes  hemorrhagic  peritonitis,  74 
Tubercular  abscess,  197 
Tuberculosis  (also  bacillus  of  tuberculosis)^ 

156 

bacillus  of,  its  discovery,  156 
caused  by  skin-grafts,  167 
diagnosis  of,  by  inoculation,  186 


INDEX    OF    SUBJECTS. 


265 


Tuberculosis,     entrance    of    bacillus    of, 

through  wounds,  167 
influence  of  trauma  on  localization  of 

bacillus  of,  41, 164 
inoculation,  163 

experiments,  159 
miliary    diffuse,    following    operative 

treatment,  42, 181,  182,  185 
of  bones,  181 

always  secondary,  181 
changes  in,  182 
of  genital  organs,  192 
of  joints,  184 
of  lymphatic  glands,  175 

spontaneous  cure  due  to  sup- 
puration, 177 
treatment  of,  180 
of  mamma,  194 
of  mouth,  191 
of  peritoneum,  189 

treatment  of,  190 
of  skin,  170 
of  tendon  sheaths,  187 
of  uterus,  192 
scrofula  identical  with,  160 
surgical,  170 


Tuberculosis,  syphilis  in  relation  to,  49 
through  skin  abrasion,  159,  163 
verrucosa  cutis,  170 

Tumor  albus,  184 

Tumors,  alleged  microbic  origin  of,  249 
myomatous,  microorganisms  in,  255 


UEINE    (aseptic),   innocuous   to    perito- 
neum, 76 
micrococci  in,  115 
microorganisms  excreted  in,  64 
of  malaria  infections,  65 
of  scarlatina  infections,  65 
of  typhus  recurrens  infections,  65 
of  varicella  infections,  65 
Uterus,  tuberculosis  of,  192 


TTARICELLA  infections,  urine  of,  65 
*      Vibrion  septique,  111,  114 
Vulvo-vaginitis,  gonococci  in,  239 


w 


OUNDS,  tubercular  infection  of,  167 


INDEX  OF  AUTHORS. 


A  HLFELD,  21 
-ti     Albarran,  255 
Albert,  214 
Andromico,  244 
Anger,  142 
Angerer,  118 
Arloing,  107,  161 
Asehoff,  52 
Aubert,  173 


202 


BABES,  50,  63,  82 
Babtchinsky,  132 
Bacelli,  155 
Baert,  142 
Bahrdt,  48,  100 
Ballance,  250 
Baranski,  215 
Barbier,  193 
Bary,  de,  89,  92,  93 
Bauragarten,  251 
Becker,  44 
Beger,  187 
Bender,  173 

Bergmann,  117,  118,  237 
Besser,  112,  126 
Bessnier,  173 
Betoli,  142 
Beumer,  147,  150 
Biedert,  131 
Billroth,  129 
Biondi,  95 

Birch-Hirschfeld,  243 
Birck,  118 
Bizzozero,  27 
Block,  173 
Blumberg,  118 
Bockhardt,  86,  233 
Boeck,  172 


Bokai,  233 

Bollinger,  22,  66,  161,  199,  204,  213,  228 

Bonome,  109,  137,  145,  150 

Bordini,  137 

Bostrb'm,  215 

Bouilly,  183 

Brauell,  199 

Brieger,  48,  49,  119,  151 

Bruns,  70,  132 

Buchner,  32,  61,  202 

Bumm,  49,  66,  232 


/1ADENE,  35 

V     Canali,  227 

Carle,  145 

Cavel,  186,  246 

Celli,  34 

Chamberland,  22 

Charrin,  32 

Chaveau,  37,  107,  111,  206 

Cheyne,  Watson,  28,  69,  88,  95,  111,  238 

Chiari,  224 

Chotzen,  248 

Christmas-Dircking-Holmfeld,  60 

Ciarrocchi,  108 

Clado,  138 

Cornet,  34,  159,  192 

Cornevin,,  202 

Cornil,  28,  160,  210 

Councilman,  93 

Coze,  114 

Czerny,  167 


DAEIER,  255 
Darwin,  113 
Davaine,  113,  199 

Delafield,  178 


268 


INDEX    OF    AUTHORS. 


Delafond,  199 

Demme,l72, 174 

Disse,  24,  245 

Doutrelepont,  160,  174,  242,  243,  244 

248 

Dowdeswell,  115 
Doyen,  135,  137 
Durante,  34 


T?DELBERG,  118 
iJ     Ehrlich,  48,  49,  99, 129 
Eiselsberg,  33,  148,  165 
Elsenberg,  168 
Emmerich,  33,  68 
Ernst,  67,  84 
Escherich,  66 
Eve,  162,  245 


FARDEL,  63 
Fehleisen,  76,  86,  129, 130,  131 
Fehling,  190 
Feltz,  114 
Finger,  170 
Firket,  218 
Fliigge,  144 
Fodor,  26,  27 
Francke,  250 

Frankel,  44,  48,  76,  98,  119,  179,  239 
Frankland,  31 
Freudenberg,  48 
Friedlander,  171 


pAFFKY,  114 

vJ     Galippe,  255 

Garre,  70,  86,  97,  100,  102,  198 

Gaucher,  32 

Gautier,  111 

Geppert,  «L,  30 

Giordano,  148 

Godwin,  108 

Goldschmidt,  149 

Gottstein,  242 

Grawitz,  77,  89,  92,  94,  97 

Griffith,  174 

Guarnieri,  34 

Gussenbauer,  53,  55 

Gusserow,  134 

Guttmann,  117 


ff 


-AAB,  236,  237 
Haberkprn,  245 

Habermann,  175 
247,  !  Hahn,  252 

Hajeck,  135 

.Hammonic,  243 

Hanau,  226,  263 

Hankin,  201 

Hanot,  165 

Haslund,  237 

Hauser,  27,  119 

Hess,  60 

Hesse,  32 

Heubner,  28,  48,  100 

Heusinger,  199 

Hiller,  118 

Hirschberger,  66 

Hochenegg,  213,  220,  221,  224 

Hochsinger,  145,  247 

Hoffa,  100,  121,  204,237 
|  Hofmokl,  168 
I  Hoist,  165 

Huber,  38,  49 

Hueppe,  64 

Hueter,  110, 187 


ISRAEL,  J.,  213,216,  221 
I     Israel,  0.,  215,  219 


JAEFE,  108 
Jani,  Curt,  20 
Janicke,  131 
Janowski,  95 
I  Jensen,  217 
Johne,  217 
Jouin, 194 
Jurgensen,  112,  122 


KAHLDEN,  138 
Kaloff,  206 
Kammerer,  237 
Kanzler,  183 
Kaposi,  220 
Kapper,  219 
Karth,  32 
Kassowitz,  247 
Kaufmann,  P.,  94 
Keller,  229 


INDEX    OF    AUTHORS. 


269 


Kelly,  142 

Kircher,  113 

Kitasato,  144,  151 

Kitt,  209 

Klebs,  18,  31,  35,  79,  80, 110,  243,  256 

Kleeblatt,  131 

Klein,  125 

Klemperer,  91,  247 

Koch,  R.,  48,  64,  113,  114,  118,  124,  129, 

156,  159 

Koch,  W.,  108,  203 
Kocher,  44,  45,  47,  101 
Kolisko,  247 

Konig,  162, 168, 182,  188 
Konjajeff,  64 
Kotschau,  193 
Koubassoff,  22 
Kranzfeld,  100,  209,  210 
Kraske,  103,  196 

Krause,  44, 100, 101, 130, 174, 183,  232 
Kreis,  232 
Kroner,  23 
Kiimmell,189 
Kuttner,212 


LAKER,  228 
Lande,  205 
Landouzy,  255 
Langenbeck,  54 
Langhans,  226 
Larger,  142 
Laruelle,  77 
Lebedeff,  20,  194 
Lebert,  47 
Ledderhose,  84 
Legrain,  230 
Lehmann,  168 
Leistikow,  240 
Leloir,  160,  163 
Lemaire,.113 
Lennander,  166 
Leser,  220 
Letulle,  183 
Letzerich,  129 
Leube,  122 
Leuwenhoek,  113 
Levy,  23 
Leyden,  97,  108 
Lindfors,  189,  191 
Lindt,  228 


Lingard,  245 
Litten,  122 
Loffler,  49,  206 
Longard,  96 
Loven, 235 
Lubarsch,  63 
Liibbert,  »1,  103 
Luecke,  41 
Luening,  226 
Lukomsky,  129 
Lumniczer,  151 
Lundgren,  210 
Lustgarten,  241 
Lustig,  157 


MAAS,  119 
Magny,  164 
Malet,  35 

Mangeri,  Romeo,' 24 
Marchand,  21 
Marcus,  245 
Markuse,  244 
Martineau,  243 
Mattel,  69 
Matterstock,  244 
Mazzuschelli,  154 
Meisels,  157 
Merklen,  165 
Metschnikoff,  56,  59 
Meyer,  168 
Middeldorpff,  167 
Mikulicz,  118 
Miquel,  31 
Mogling,  157,  183 
Monpurgo,  64 
Moosbrugger,  213,  228 
Miiller,  102,  162,  182,  183 
Muskatbliith,  39 


NAEGELI,  36,  113,  199 
Nathan,  94 
Neelsen,  121,  132 
Neisser,  131,1171,  230,  255 
Nencki,  209 
Nepveau,  54,  129 
Netter,  21 

Neumann,  32,  64,  69 
Nicaise,  188 
Nicolaier,  36,  143,  144 


270 


INDEX    OF    AUTHORS. 


Nicolas,  34 
Nocard,  159 
Noorden,  von,  136 
Nuttal,  61 


OGSTON,  80,  115 
Ohlmuller,  149 
Okinschitz,  127 
Orloff,  52 

Orth,  43,  76,  98,  129 
Orthmann,  93,  194 


pAGENSTECHEE,  160 

I      Paget,  249 

Paltauf,  170 

Panum,  116 

Partsch,  213,  220 

Passet,  80,  81,  82,  84,  85,  130 

Pasteur,  113 

Patterson,  258 

Pawlowsky,  68,  74,  125,  126 

Pernice,  34 

Perty,  113 

Petri,  33 

Pettenkofer,  29 

Pfeiffer,  160,  174,  251 

Philipowicz,  64 

Piana,217 

Pollender,  199 

Ponfick,  213 

Pott,  239 

Poulet,  188 


Q 


UINQUAUD,  173 


RANKE,  141 
Easkina,  83 
Eassdnitz,  172 
Eattone,  145 
Eaymond,  164 
Eecklinghausen,  110 
Eenken, 183 
Eenouard,  173 
Eheiner,  137 
Eibbert,  44,  57,  62,  67,  103 


Eiedel,  187 

Eiehl,  170 

Eindfleisch,  110 

Einne,  44,  51,  54,  78,  104,  121 

Eodet,  102 

Eosenbach,  21,  43,  44,  45,  49,  80,  82,  83, 

84,  101,  110,  126,  139,  143,  144,  H45 
Eosenberger,  120 
Eosenstein,  63 
Rotter,  214,  21 6 
Eoux,  159 
Ruflfer,  62 
Euiys,  95 
Eussel,  256 
Eutimeyer,  228 


SACHS,  173 
Sahli,  238 
Saltzman,  195 
Samter,  48 
Samuel,  118 
Sangalli,  21 
Siinger,  44,  238 
Scheuerlen,  90,  93,  250 
Schlegtendal,  157,  198 
Schliferowitsch,  191 
Schmidt,  163 
Schnell,  181 
Schnitzler,  49 
Schuchardt,  174,  183 
Schueller,  41,  126,  159,  171 
Schiitz,  206,  242 
Schwarz,  236 
Schweiger,  65 
Schwimmer,  69,  132 
Seitz,  64 
Selini,  117 
Semmer,  117 
Senasy,  227 
Senator,  99 
Senger,  251 
Shattock,  250 
Simone,  137 
Sinclair,  235 
Sirena,  34 
Sjoring,  256 
Slessarewskji,  204 
Smirnoff,  138,  238 
Smith,  115 
Socin,  55 


INDEX    OF    AUTHOES. 


271 


Soltmann,  217 
Sormani,  154 
Soyka,  35 
Spaeth,  239 
Stein  Schneider,  239 
Steinthal,  46 
Sternberg,  29,  114,  240 
Strauss,  22,  32 
Struck,  101 
Strumpell,  197 
Szuman,  41 


rpAGUCHI,  24,  245 

1     Tavel  (also  Gavel),  186,  246 

Thiriar,  142 

Thoma,  72,  252,  256 

Thomas,  202 

Tiegel,  121 

Tillmanns,  129,  137 

Tricomi,  88,  106 

Trousseau,  J33 

Trzebicky,  190 

Tschering,  166 

Tyndall,  32 


TTLLMANN,  196 
LJ      Uskoff,  93 


T7ERCHIERE,  42 
'       Verhoogen,  142 
Verneuil,  138 
Vidal,  112 


Vierhoff,  203 
Vierordt,  191 
Villard,  188 
Villemin,  156 
Volkmann,  41,  187 


WAHL,  167 
Waldeyer,  110 
Wartmann,  42,  186 
Wegner,  77 
Wehde,  34 
Wehr,  61,  254 

Weichselbaum,  77,  98,  157,  177 
Weigert,  177 
Welander,  231,  233 
Wells,  Spencer,  190 
Werth,  193 
Whitney,  131 
Wickham,  256 
Widmark,  236 
Wilde,  129 
Williams,  Theo.,  34 
Winckel,  134 
Wolf,  M.,  216 
Wolff,  Max,  22,  137 
Woolbridge,  201 
Woronzoff,  30 
Wyssokowitsch,  43,  56 


|  r/AHOR,  27 
LJ     Zeissl,  245 

|  Zemann,  225 
Zuckermann,  87 
i  Zweigbaum,  192 


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ble a  reduction  in  the  price  of  THE  NEWS  to  Four  Dollars  per  year,  so  that  it  is  now 
by  far  the  cheapest  as  well  as  the  best  large  weekly  journal  published  in  America. 

By  means  of  THE  MEDICAL  NEWS  every  physician  is  now  able  at  a  minimum  outlay 
to  insure  his  own  receipt  of  the  earliest  and  most  authoritative  information  on  all  subjects 

(Continued  on  next  noae.) 


2    LEA  BROTHERS  &  Co.'s  PERIODICALS — Am.  Journal,  Medical  News. 
THE   MEDICAL   NEWS— Continued. 

of  interest  to  the  great  medical  world.  The  foremost  writers,  teachers  and  practitioners 
of  the  day  furnish  original  articles,  clinical  lectures  and  notes  on  practical  advances; 
the  latest  methods  in  leading  hospitals  are  promptly  reported ;  a  condensed  summary  of 
progress  is  gleaned  each  week  from  a  large  exchange  list,  comprising  the  best  journals 
at  home  and  abroad ;  a  special  department  is  assigned  to  abstracts  requiring  full  treat- 
ment for  proper  presentation  ;  editorial  articles  are  secured  from  writers  able  to  deal 
instructively  with  questions  of  the  day;  books  are  carefully  reviewed;  society  proceedings 
are  represented  by  the  pith  alone ;  regular  correspondence  is  furnished  by  gentlemen  in 
position  to  know  all  occurrences  of  importance  in  the  district  surrounding  important 
medical  centres,  and  minor  matters  of  interest  are  grouped  each  week  under  news  items. 
Everything  is  presented  with  such  brevity  as  is  compatible  with  clearness,  and  in  the 
most  attractive  manner.  In  a  word  THE  MEDICAL  NEWS  is  a  crisp,  fresh,  weekly  news- 
paper and  as  such  occupies  a  well-marked  sphere  of  usefulness,  distinct  and  comple- 
mentary to  the  ideal  monthly  magazines,  THE  AMERICAN  JOURNAL  OF  THE  MEDICAL 
SCIENCES. 


Tie  American  journal  of  *SB  Medical  j3cience$ 

Published  Monthly,  at  Four  Dollars  Per  Annum 

Enters  upon  its  seventy-second  year  ( 1891)  with  assurances  of  increased  usefulness.  Encour- 
aged by  the  emphatic  endorsement  of  the  profession,  as  indicated  by  a  growth  in  its  subscrip- 
tion list  of  fifty  per  cent,  since  its  appearance  as  a  monthly  at  a  reduced  price,  those  in  charge 
will  spare  no  effort  to  maintain  its  place  as  the  leader  of  medical  periodical  literature- 
Being  the  medium  chosen  by  the  best  minds  of  the  profession  during  the  past  seventy 
years  for  the  presentation  of  their  ablest  papers,  THE  AMERICAN  JOURNAL  has  well 
earned  the  praise  accorded  it  by  an  unquestioned  authority — "  from  this  file  alone,  were 
all  other  publications  of  the  press  for  the  last  fifty  years  destroyed,  it  would  be  possible  to 
reproduce  the  great  majority  of  the  real  contributions  of  the  world  to  medical  science 
during  that  period."  Original  Articles,  Ke  views  and  Progress,  the  three  main  departments 
into  which  the  contents  of  THE  JOURNAL  are  divided,  will  be  found  to  possess  still  greater 
interest  than  in  the  past.  The  brightest  talent  on  both  sides  of  the  Atlantic  is  enlisted  in 
its  behalf  and  no  effort  will  be  spared  to  make  THE  JOURNAL  more  than  ever  worthy  of 
its  position  as  the  representative  of  the  highest  form  of  medical  thought. 


COMMUTATION  RATE. 

Taken  together,  THE  JOURNAL  and  NEWS  form  a  peculiarly  useful  combination, 
and  afford  their  readers  the  assurance  that  nothing  of  value  in  the  progress  of  medical 
matters  shall  escape  attention.  To  lead  every  reader  to  prove  this  personally  the  com- 
mutation rate  has  been  placed  at  the  exceedingly  low  figure  of  $7.50. 


SPECIAL  OFFERS. 

The  MEDICAL  NEWS  VISITING  LIST  (regular  price,  $1.25,  see  next  page,)  or  The 
Year-Book  of  Treatment  (regular  price,  $1.50,  see  page  17,)  will  be  furnished  to  advance- 
paying  subscribers  to  either  or  both  of  these  periodicals  for  75  cents  apiece  ;  or  Journal, 
News,  Visiting  List  and  Year-Book,  $8.50. 


Subscribers  can  obtain,  at  the  close  of  each  volume,  cloth  covers  for  THE  JOURNAL  (one 
annually),  and  for  THE  NEWS  (one  annually),  free  by  mail,  by  remitting  Ten  Cents  for  THE 
JOURNAL  cover,  and  Fifteen  Cents  for  THE  NEWS  cover. 


'The  safest  mode  of  remittance  is  by  bank  check  or  postal  money  order,  drawn  to 
the  order  of  the  undersigned ;  where  these  are  not  accessible,  remittances  for  subscriptions 
may  be  sent  at  the  risk  of  the  publishers  by  forwarding  in  registered  letters.  Address, 

LEA  BROTHERS  &  CO.,  706  &  708  Sansom  Street,  Philadelphia. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Period.,  Manuals.  3 

THE  MEDICAL  NEWS  VISITING  LIST  FOR  1891 

Is  published  in  four  styles,  "Weekly  (dated  for  30  patients) ;  Monthly  (undated,  for  120 
patients  per  month)  ;  Perpetual  (undated,  for  30  patients  weekly  per  year) ;  and  Per- 
petual (undated,  for  60  patients  weekly  per  year).  The  60-patient  Perpetual  is  a  nov- 
elty for  1891,  and  consists  of  256  pages  of  assorted  blanks.  The  first  three  styles 
contain  32  pages  of  important  data  and  176  pages  of  assorted  blanks.  Each  style  is  in 
one  wallet-shaped  book,  leather-bound,  with  pocket,  pencil,  rubber,  erasable  tablet  and 
catheter-scale.  Price,  each,  $1.25. 

SPECIAL  COMBINATIONS  WITH  VISITING  LIST. 

THE  AMEB.  JOURNAL  ($4)  with  VISITING  LIST  ($1.25),  or  YEAR-BOOK  ($1.50),  for  $4.75 
THE  MEDICAL  NEWS  ($4)  "  «  "  '  «  "  "  «  "  4.75 

THE  JOURNAL  AND  NEWS  ($7.50)       "  "  "    8.25 

THE  JOURNAL,  NEWS,  VISITING  LIST  and  YEAR-BOOK  (see  page  17),      .        .         8.50 

This  list  is  all  that  could  be  desired.    It  con-    list  of  diseases  arranged  alphabetically,  giving 
tains  a  vast  amount  of  useful  information,  especi- 


and  therapeutics.— Canadian  Practitioner. 


1  doses 


It  is  a  masterpiece.  Some  of  the  features  are 
peculiar  to  "  The  Medical  News  Visiting  List," 
notably  the  Therapeutic  Table,  prepared  from  Dr. 
T.  Lauder  Brunton's  book,  which  contains  the 


under  each  a  list  of  the  prominent  drugs  em- 
ployed in  the  treatment.  When  ordered,  a  Ready 
Reference  Thumb-letter  Index  is  furnished.  This 
is  a  feature  peculiar  to  this  Visiting  List.— Physi- 
cian and  Surgeon,  December. 

For  convenience  and  elegance  it  is  not  surpass- 
Able.— Obstetric  Gazette,  November. 


THE  MEDICAL  NEWS  PHYSICIANS'  LEDGER. 

Containing  300  pages  of  fine  linen  "  ledger  "  paper,  ruled  so  that  all  the  accounts  of  a 
large  practice  may  be  conveniently  kept  in  it,  either  by  single  or  double  entry,  for  a  long 
period.  Strongly  bound  in  leather,  with  cloth  sides,  and  with  a  patent  flexible  back, 
which  permits  it  to  lie  perfectly  flat  when  opened  at  any  place.  Price,  $4.00. 


HARTSHORNE,  HENRY,  A.  M.,  M.  &.,  LL.  D., 

Lately  Professor  of  Hygiene  in  the  University  of  Pennsylvania. 

A  Conspectus  of  the  Medical  Sciences ;  Containing  Handbooks  on  Anatomy, 
Physiology,  Chemistry,  Materia  Medica,  Practice  of  Medicine,  Surgery  and  Obstetrics. 
Second  edition,  thoroughly  revised  and  greatly  improved.  In  one  large  royal  12mo. 
volume  of  1028  pages,  with  477  illustrations.  Cloth,  $4.25 ;  leather,  $5.00. 

industry  and  energy  of  its  able  editor.— .Boston 
Medical  and  Surgical  Journal,  Sept.  3. 1874. 

We  can  say  with  the  strictest  truth  that  it  is  the 
best  work  of  the  kind  with  which  we  are  ac- 
quainted. It  embodies  in  a  condensed  form  all 
recent  contributions  to  practical  medicine,  and  is 
therefore  useful  to  every  busy  practitioner  through- 
out our  country,  besides  being  admirably  adapted 
to  the  use  of  students  of  medicine.  The  book  is 
faithfully  and  ably  executed. — Charleston  Medical 
Journal,  April,  1875. 


The  object  of  this  manual  is  to  afford  a  conven- 
ient work  of  reference  to  students  during  the  brief 
moments  at  their  command  while  in  attendance 
upon  medical  lectures.  It  is  a  favorable  sign  that 
it  has  been  found  necessary,  in  a  short  space  of 
time,  to  issue  a  new  and  carefully  revised  edition. 
The  illustrations  are  very  numerous  and  unusu- 
ally clear,  and  each  part  seems  to  have  received 
its  due  share  of  attention.  We  can  conceive  such 
a  work  to  be  useful,  not  only  to  students,  but  to 
practitioners  as  well.  It  reflects  credit  upon  the 


NEILL,  JOHN,  M.  D.,  and  SMITH,  F.  G.,  M.  D., 

Late  Surgeon  to  the  Penna.  Hospital.  Prof,  of  the  Institutes  of  Med.  in  the  Univ.  of  Penna. 

An  Analytical  Compendium  of  the  Various  Branches  of  Medical 
Science,  for  the  use  and  examination  of  Students.  A  new  edition,  revised  and  improved. 
In  one  large  royal  12mo.  volume  of  974  pages,  with  374  woodcuts.  Cloth,  $4 ;  leather,  $4.75. 

LUDLOW,  J.L.,M.D., 

Consulting  Physician  to  the  Philadelphia  Hospital,  etc. 

A  Manual  of  Examinations  upon  Anatomy,  Physiology,  Surgery,  Practice  of 
Medicine,  Obstetrics,  Materia  Medica,  Chemistry,  Pharmacy  and  Therapeutics.  To  which 
is  added  a  Medical  Formulary.  Third  edition,  thoroughly  revised,  and  greatly  enlarged.  In 
one  12mo.  volume  of  816  pages,  with  370  illustrations.  Cloth,  $3.25 ;  leather,  $3.75. 

The  arrangement  of  this  volume  in  the  form  of  question  and  answer  renders  it  espe- 
cially suitable  for  the  office  examination  of  students,  and  for  those  preparing  for  graduation 

HOBLTN,  KICHAItD  D.,  M.  D. 

A  Dictionary  of  the  Terms  Used  in  Medicine  and  the  Collateral 
Sciences.  Kevised,  with  numerous  additions,  by  ISAAC  HAYS,  M.  D.,  late  editor  of 
The  American  Journal  of  the  Medical  Sciences.  In  one  large  royal  12mo.  volume  of  520 
double-columned  pages.  Cloth,  $1.50 ;  leather,  $2.00. 

It  is  the  best  book  of  definitions  we  have,  and  ought  always  to  be  upon  the  student's  table—  Southern 
Medical  and  Surgical  Journal. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS— Dictionaries. 
JUST    READY. 


THE 


INCLUDING 


English,  French,  German,  Italian  and  Latin  Technical  Terms  used  in  Medicine  and 
the  Collateral  Sciences,  and  a  Series  of  Tables  of  Useful  Data. 


BY 


John  ,  Billing?,  IJ.D,  LL.D,  Ediq.  and  Haflr,,  D.C.L,  Dpi, 

Member  of  the  National  Academy  of  Sciences,  Surgeon  U.  S.  A.t  etc. 
WITH  THE  COLLABORATION  OF 


PROF.  W.  O.  ATWATER.  JAMES  M.  FLINT,  M.  D., 

FRANK  BAKER,  M.  D.,  J.  H.  KIDDER,  M.  D., 

S.  M.  BURNETT,  M.  D.,  WILLIAM  LEE,  M.D., 

W.  T.  COUNCILMAN,  M.  D.,  R.  LORINI,  M.  D., 


WASHINGTON  MATTHEWS,  M.  D. 
C.  S.  MINOT,  M.D. 
H.  C.  YARROW,  M.  D., 


In  two  very  handsome  royal  octavo  volumes  containing  1574  pages, 
with  two  colored  plates. 

Per  Volume— Cloth,  $6;   Leather,  $7,'    Half  Morocco,  Marbled  Edges,  $8.5O.    For  Sale 
by  Subscription  only.    Specimen  pages  on  application.    Address  the  Publishers. 


The  publishers  have  great  pleasure  in  presenting  to  the  profession  a  new  practical 
working  dictionary  embracing  in  one  alphabet  all  current  terms  used  in  every  depart- 
ment of  medicine  in  the  five  great  languages  constituting  modern  medical  literature. 

For  the  vast  and  complex  labor  involved  in  such  an  undertaking  no  one  better  quali- 
fied than  Dr.  Billings  could  have  been  selected.  He  has  planned  the  work,  chosen  the 
most  accomplished  men  to  assist  him  in  special  departments,  and  personally  supervised 
and  combined  their  work  into  a  consistent  and  uniform  whole. 

Special  care  has  been  taken  to  render  the  definitions  clear,  sharp  and  concise. 
They  are  given  in  English,  with  synonyms  in  French,  German  and  Italian  of  the  more 
important  words  in  English  and  Latin. 

Eegarded  as  a  dictionary,  therefore,  this  standard  work  supplies  the  physician, 
surgeon  and  specialist  with  all  information  concerning  medical  words,  simple  and  com- 
pound, found  in  English,  giving  correct  spelling,  clear,  sharp  definitions  and  accentua- 
tion, and  furthermore  it  enables  him  to  consult  foreign  works  and  to  understand  the  large 
and  increasing  number  of  foreign  words  used  in  medical  English.  It  is  especially  fall 
in  phrases  comprising  two,  three  or  more  words  used  in  special  senses  in  the  various 
departments  of  medicine. 

The  work  is,  however,  far  more  than  a  dictionary,  and  partakes  of  the  nature  of  an 
encyclopaedia,  as  it  gives  in  its  body  a  large  amount  of  valuable  therapeutical  and  chemi- 
cal information,  and  groups  in  its  tables,  in  a  condensed  and  convenient  form,  a  vast 
amount  of  important  data  which  will  be  consulted  daily  by  all  in  active  practice. 

The  completeness  of  the  work  is  made  evident  by  the  fact  that  it  defines  84,844 
separate  words  and  phrases. 

The  type  has  been  most  carefully  selected  for  boldness  and  clearness,  and  everything 
has  been  done  to  secure  ease,  rapidity  and  durability  in  use. 

Its  scope  is  one  which  will  at  once  satisfy  the 
student  and  meet  all  the  requirements  of  the  med- 
ical practitioner.  Clear  and  comprehensive  defi- 
nitions of  words  should  form  the  prime  feature  of 
any  dictionary,  and  in  this  one  the  chief  aim 
se*>ms  to  be  to  give  the  exact  signification  and  the 
different  meanings  of  terms  in  use  in  medicine 
and  the  collateral  sciences  in  language  as  terse  as 
is  compatible  with  lucidity.  The  utmost  brevity 
and  conciseness  have  been  kept  in  view.  The  work 
is  remarkable,  too,  for  it?  fulness.  The  enumera- 
tions and  subdivisions  under  each  word  heading 
are  strikingly  complete,  as  regardsalike  the  Eng 
lish  tongue  and  the  languages  chiefly  employed 
by  ancient  and  modern  science.  It  is  impossible 
to  do  justice  to  the  dictionary  by  any  casual  illus 
tration.  It  presents  to  the  English  reader  a 
thoroughly  scientific  mode  of  acquiring  a  rich 
vocabulary  and  offers  an  accurate  and  ready  means 
of  reference  in  consulting  works  in  any  of  the 


three  modern  continental  languages  which  are 
richest  in  medical  literature.  To  add  to  its  use- 
fulness as  a  work  of  reference  some  valuable 
tables  are  given.  Another  feature  of  the  work  is 
the  accuracy  of  its  definitions,  all  of  which  have 
been  checked  by  comparison  with  many  other 
standard  works  in  the  different  languages  it  deals 
with.  Apart  from  tne  boundless  stores  of  informa- 
tion which  may  be  gained  by  the  study  of  a  good 
dictionary,  one  is  enabled  by  the  work  under  notice 
to  read  intelligently  any  technical  treatise  in  any 
of  the  four  chief  modern  languages.  There  can- 
not be  two  opinions  as  to  the  great  value  and  use- 
fulness of  this  dictionary  as  a  oook  of  ready  refer- 
ence for  all  sorts  and  conditions  of  medical  men. 
So  far  as  we  have  been  able  to  see,  no  subject  has 
been  omitted,  and  in  respect  of  completeness  it  will 
be  found  distinctly  superior  to  any  medical  lexicon 
yet  published.—  The  London  Lancet,  April  5, 1890. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS— Anatomy.  5 

GRAY,  HENRY,  F.  R.  S., 

Lecturer  on  Anatomy  at  St.  George's  Hospital,  London. 

Anatomy,  Descriptive  and  Surgical.  Edited  by  T.  PICKERING  PICK, 
F.  R.  C.  S.j  Surgeon  to  and  Lecturer  on  Anatomy  at  St.  George's  Hospital,  London, 
Examiner  in  Anatomy,  Royal  College  of  Surgeons  of  England.  A  new  American  from 
the  eleventh  enlarged  and  improved  London  edition,  thoroughly  revised  and  re-edited 
fey  WILLIAM  W.  KEEN,  M.  D.,  Professor  of  Surgery  in  the  Jefferson  Medical  College  of 
Philadelphia.  To  which  is  added  the  second  American  from  the  latest  English  edition  of 
LANDMARKS,  MEDICAL  AND  SURGICAL,  by  LUTHER  HOLDEN,  F.  R.  C.  S.  In  one  imperial 
octavo  volume  of  1098  pages,  with  685  large  and  elaborate  engravings  on  wood.  Price  of 
edition  in  black:  Cloth,  $6;  leather,  $7;  half  Russia,  $7.50.  Price  of  edition  in  colors 
(see  below):  Cloth,  $7.25;  leather,  $8.25 ;  half  Russia,  $8.75. 

This  work  covers  a  more  extended  range  of  subjects  than  is  customary  in  the  ordinary 
text-books,  giving  not  only  the  details  necessary  for  the  student,  but  also  the  application  to 
those  details  to  the  practice  of  medicine  and  surgery.  It  thus  forms  both  a  guide  for  the 
learner  and  an  admirable  work  of  reference  for  the  active  practitioner.  The  engraving 
form  a  special  feature  in  the  work,  many  of  them  being  the  size  of  nature,  nearly  all 
original,  and  having  the  names  of  the  various  parts  printed  on  the  body  of  the  cut,  in 
place  of  figures  of  reference  with  descriptions  at  the  foot.  In  this  edition  a  new  departure 
has  been  taken  by  the  issue  of  the  work  with  the  arteries,  veins  and  nerves  distinguished 
by  different  colors.  The  engravings  thus  form  a  complete  and  splendid  series,  which  will 
greatly  assist  the  student  in  forming  a  clear  idea  of  Anatomy,  and  will  also  serve  to  refresh 
the  memory  of  those  who  may  find  in  the  exigencies  of  practice  the  necessity  of  recall- 
ing the  details  of  the  dissecting-room.  Combining,  as  it  does,  a  complete  Atlas  of 
Anatomy  with  a  thorough  treatise  on  systematic,  descriptive  and  applied  Anatomy, 
the  work  will  be  found  of  great  service  to  all  physicians  who  receive  students  in  their 
offices,  relieving  both  preceptor  and  pupil  of  much  labor  in  laying  the  groundwork  of  a 
thorough  medical  education. 

For  the  convenience  of  those  who  prefer  not  to  pay  the  slight  increase  in  cost  necessi- 
tated by  the  use  of  colors,  the  volume  is  published  also  in  black  alone,  and  maintained 
in  this  style  at  the  price  of  former  editions,  notwithstanding  its  largely  increased  size. 

Landmarks,  Medical  and  Surgical,  by  the  distinguished  Anatomist,  Mr.  Luther  Holden, 
has  been  appended  to  the  present  edition  as  it  was  to  the  previous  one.  This  work  gives 
in  a  clear,  condensed  and  systematic  way  all  the  information  by  which  the  practitioner  can 
determine  from  the  external  surface  of  the  body  the  position  of  internal  parts.  Thus 
complete,  the  work  will  furnish  all  the  assistance  that  can  be  rendered  by  type  and 
illustration  in  anatomical  study. 

The  most  popular  work  on  anatomy  ever  written,  books.  The  work  is  published  with  black  and 
is  sufficient  to  say  of  it  that  this  edition,  thanks  colored  plates.  It  is  a  marvel  of  book-making.— 
its  American  editor,  surpasses  alj_  other  edi-  American  Practitioner  and  News,  Jan.  21, 1888. 

Gray's  Anatomy  is  the  most  magnificent  work 
upon  anatomy  which  has  ever  been  published  in 
the  English  or  any  other  language. — Cincinnati 
Medical  News,  Nov.  1887. 

As  the  book  now  goes  to  the  purchaser  he  is  re- 
ceiving the  best  work  on  anatomy  that  is  published 
in  any  language. —  Virginia  Med.  Monthly,  Dec.  1887. 
Gray's  standard  Anatomy  has  been  and  will  be 
for  years  the  text-book  for  students.  The  book 
needs  only  to  be  examined  to  be  perfectly  under- 
stood.—Medical  Press  of  Western  New  York,  Jan. 


It  is  sufficient 
to 

tions.  —  Jour,  of  the  Amer.  Med.  Ass'n,  Dec.  31,  1887. 
A  work  which  for  more  than  twenty  years  has 
had  the  lead  of  all  other  text-books  on  anatomy 
throughout  the  civilized  world  comes  to  hand  in 
such  oeauty  of  execution  and  accuracy  of  text 
•and  illustration  as  more  than  to  make  good  the 
large  promise  of  the  prospectus.  It  would  be  in- 
deed difficult  to  name  a  feature  wherein  the  pres- 
ent American  edition  of  Gray  could  be  mended 
or  bettered,  and  it  needs  no  prophet  to  see  that 
the  royal  work  is  destined  for  many  years  to  come 


y 
ld 


Co  hold  the  first  place  among  anatomical  text- 


ALSO  FOR  SALE  SEPARATE  — 

HOLI>EN,  LUTHER,  F.  JR.  C.  S., 

Surgeon  to  St.  Bartholomew's  and  the  Foundling  Hospitals,  London. 
Landmarks,  Medical  and  Surgical.    Second  American  from  the  latest  revised 


English  edition,  with  additions  by  W.  WT  KEEN,  M.  D.,  Professor  of  Artistic  Anatomy  in 
the  Penna.  Academy  of  Fine  Arts.     In  one  12mo.  volume  of  148  pages.     Cloth,  $1.00. 


DTTNGLISON,  ROBLEY,  M.D., 

Late  Professor  of  Institutes  of  Medicine  in  the  Jefferson  Medical  College  of  Philadelphia. 


OffV 

prudence  and'  Dentistry,  Notices  of  Climate  and  of  Mineral  Waters,  Formulae  for  Officinal, 
Empirical  and  Dietetic  Preparations,  with  the  Accentuation  and  Etymology  of  the  Terms, 
and  the  French  and  other  Synonymes,  so  as  to  constitute  a  French  as  well  as  an  English 
Medical  Lexicon.  Edited  by  RICHARD  J.  DUNGLISON,  M.  D.  In  one  very  large  and 
handsome  royal  octavo  volume  of  1139  pages.  Cloth,  $6.50 ;  leather,  raised  bands,  $7.50 ; 
very  handsome  half  Russia,  raised  bands,  $8. 

It  has  the  rare  merit   that  it  certainly  has  no  rival   in  the  English  language  for  accuracy 
and  extent  of  references.— London  Meaical  Gazette. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Anatomy. 


ALLEN,  HARRISON,  M.  &., 

Professor  of  Physiology  in  the  University  of  Pennsylvania. 

A  System  of  Human  Anatomy,  Including  Its  Medical  and  Surgical 
Relations.  ^  For  the  use  of  Practitioners  and  Students  of  Medicine.  With  an  Intro- 
ductory Section  on  Histology.  By  E.  O.  SHAKESPEAKE,  M.  D.,  Ophthalmologist  to 
the  Philadelphia  Hospital.  Comprising  813  double-columned  quarto  pages,  with  380 
illustrations  on  109  full  page  lithographic  plates,  many  of  which  are  in  colors,  and  241 
engravings  in  the  text.  In  six  Sections,  each  in  a  portfolio.  Section  I.  HISTOLOGY. 
Section  II.  BONES  AND  JOINTS.  Section  III.  MUSCLES  AND  FASCIAE.  Section  IV. 
ARTERIES,  VEINS  AND  LYMPHATICS.  Section  V.  NERVOUS  SYSTEM.  Section  VI. 
ORGANS  OF  SENSE,  OF  DIGESTION  AND  GENITO-URINARY  ORGANS,  EMBRYOLOGY, 
DEVELOPMENT,  TERATOLOGY,  SUPERFICIAL  ANATOMY,  POST-MORTEM  EXAMINATIONS, 
AND  GENERAL  AND  CLINICAL  INDEXES.  Price  per  Section,  $3.50 ;  also  bound  in  one 
volume,  cloth,  $23.00 ;  very  handsome  half  Kussia,  raised  bands  and  open  back,  $25.00. 
For  sale  by  subscription  only.  Apply  to  the  Publishers. 


It  is  to  be  considered  a  study  of  applied  anatomy 
in  its  widest  sense — a  systematic  presentation  of 
such  anatomical  facts  as  can  be  applied  to  the 
practice  of  medicine  as  well  as  of  surgery.  Our 
author  is  concise,  accurate  and  practical  in  his 
statements,  and  succeeds  admirably  in  infusing 
an  interest  into  the  stud 
sidered  a  dry  subject. 

ogy  is  treated  in  a  masterly  manner,  and  the 
ground  is  travelled  over  by  one  thoroughly  famil- 
iar with  it.  The  illustrations  are  made  with  great 


iy  of  what  is  generally  con- 
The  department  of  Histol- 


to  those  of  the  operating  surgeon.    In  fa 
general  practitioners  will  read  the  work  wi 


care,  and  are  simply  superb.  There  is  as  much 
of  practical  application  of  anatomical  points  to 
the  every-day  wants  of  the  medical  clinician  as 

fact,  few 
e  work  without  a 

feeling  of  surprised  gratification  that  so  many 
points,  concerning  which  they  may  never  have 
thought  before  are  so  well  presented  for  their  con- 
sideration. It  is  a  work  which  is  destined  to  be 
the  best  of  its  kind  in  any  language. — Medical 
Record,  Nov.  25,1882. 


CLARKE,  W.  B.,  F.R.  C.S.  &  LOCKWOOI>,  C.  B.,  F.R.  C.S. 

Demonstrators  of  Anatomy  at  St.  Bartholomew's  Hospital  Medical  School,  London. 
The  Dissector's  Manual.     In  one  pocket-size  12mo.  volume  of  396  pages,  with 
49  illustrations.    Limp  cloth,  red  edges,  $1.50.     See  Students'  Series  of  Manuals,  page  31. 

Messrs.Clarke  and  Lock  wood  have  written  a  book  intimate  association  with  students  could  have 
that  can  hardly  be  rivalled  as  a  practical  aid  to  the  given.  With  such  a  guide  as  this,  accompanied 
dissector.  Their  purpose,  which  is  "how  to  de-  I  by  so  attractive  a  commentary  as  Treves'  Surgical 
scribe  the  best  way  to  display  the  anatomical  |  Applied  Anatomy  (same  series),  no  student  could 
"  *•**  **»  K°  ^/»^»»i«  »v,,j  r,w,^.v,;>,  ,,i,,  ;^4m.^r,4nA  ;»,  *!•>». 


structure,"  has  been  fully  attained.  They  excel  in 
a  lucidity  of  demonstration  and  graphic  terseness 
of  expression,  which  only  a  long  training  and 


fail  to  be  dee 

study  of  anatomy 

gical  Journal,  April,  1884. 


ply  and  absorbingly  interested  i 
tomy.  —  New  Orleans  Medical  and 


in  the 
and  Sur- 


TREVES, FREDERICK,  F.  R.  C.  S., 

Senior  Demonstrator  of  Anatomy  and  Assistant  Surgeon  at  the  London  Hospital. 

Surgical  Applied  Anatomy.    In  one  pocket-size  12mo.  volume  of  540 
with  61  illustrations.   Limp  cloth,  red  edges,  $2.00.    See  Students'  Series  of  Manuals? 
page  31. 
He  has  produced  a  work  which  will  command 


larger  circle  of  readers  than  the  class  for  which  it 
was  written.  This  union  of  a  thorough,  practical 
acquaintance  with  these  fundamental  branches, 
quickened  by  daily  use  as  a  teacher  and  practi- 
tioner, has  enabled  our  author  to  prepare  a  work 
which  it  would  be  a  most  difficult  task  to  excel. — 
The  American  Practitioner,  Feb.  1884. 


This  number  of  the  "  Manuals  for  Students  "  is- 
most  excellent,  giving  just  such  practical  knowl 
edge  as  will " 
the  injuries 

The  book  is  intended  mainly  for  students,  but  i4 
will  also  be  of  great  use  to  practitioners.  The  illus- 
trations are  well  executed  and  fully  elucidate  the 
text.— Southern  Practitioner,  Feb.  1884. 


will  be  required  for  application  in  relieving 
iries   to  which  the  living  body  is  liable. 


BELLAMY,  EDWARD,  F.  It.  C.  S., 

Senior  Assistant-Surgeon  to  the  Charing- Cross  Hospital,  London. 

The  Student's  Guide  to  Surgical  Anatomy :  Being  a  Description  of  the 


most 
operative 


Important  Surgical  Regions  of  the  Human  Body,  and  intended  as  an  Introduction  to 
tive  Surgery.    In  one  12mo.  volume  of  300  pages,  with  50  illustrations.    Cloth,  $2.25* 

WILSON,  ERASMUS,  F.  R.  S. 

A  System  of  Human  Anatomy,  General  and  Special.  Edited  by  W.  H. 
GOBRECHT,  M.  D.,  Professor  of  General  and  Surgical  Anatomy  in  the  Medical  College  of 
Ohio.  In  one  large  and  handsome  octavo  volume  of  616  pages,  with  397  illustrations. 
Cloth,  $4.00;  leather,  $5.00. 


CLELAND,  JOHN,  M.  D.,  F.  R.  S., 

Professor  of  Anatomy  and  Physiology  in  Queen's  College,  Galway. 

A  Directory  for  the  Dissection  of  the  Human  Body. 

volume  of  178  pages.    Cloth,  $1.25. 


In  one  12mo 


HARTSHORNE'S  HANDBOOK  OF  ANATOMY 
AND  PHYSIOLOGY.  Second  edition,  revised. 
In  one  royal  12mo.  volume  of  310  pages,  with  220 
woodcuts.  Cloth,  $1.75. 


HORNER'S  SPECIAL  ANATOMY  AND  HISTOL- 
OGY. Eighth  edition,  extensively  revised  and 
modified.  In  two  octavo  volumes  of  1007  pages, 
with  320  woodcuts.  Cloth,  $6.00. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Physics,  Physio!.,  Anat. 


DRAPER,  JOHN  €.,  M.  D.,  LL.  !>., 

Professor  of  Chemistry  in  the  University  of  the  City  of  New  York. 

Medical  Physics.  A  Text-book  for  Students  and  Practitioners  of  Medicine.  In 
one  octavo  volume  of  734  pages,  with  376  woodcuts,  mostly  original.  Cloth,  $4. 

FROM  THE  PREFACE. 

The  fact  that  a  knowledge  of  Physics  is  indispensable  to  a  thorough  understanding  of 
Medicine  has  not  been  as  fully  realized  in  this  country  as  in  Europe,  where  the  admirable 
works  of  Desplats  and  Gariel,  of  Kobertson  and  of  numerous  German  writers  constitute  a 
branch  of  educational  literature  to  which  we  can  show  no  parallel.  A  full  appreciation 
of  this  the  author  trusts  will  be  sufficient  justification  for  placing  in  book  form  the  sub- 
stance of  his  lectures  on  this  department  of  science,  delivered  during  many  years  at  the 
University  of  the  City  of  New  York. 

Broadly  speaking,  this  work  aims  to  impart  a  knowledge  of  the  relations  existing 
between  Physics  and  Medicine  in  their  latest  state  of  development,  and  to  embody  in  the 
pursuit  of  this  object  whatever  experience  the  author  has  gained  during  a  long  period  of 
teaching  this  special  branch  of  applied  science. 

No  man  in  America  was  better  fitted  than  Dr. 
Draper  for  the  task  he  undertook,  and  he  has  pro- 
vided the  student  and  practitioner  of  medicine 
with  a  volume  at  once  readable  and  thorough. 
Even  to  the  student  who  has  some  knowledge  of 
physics  this  book  is  useful,  as  it  shows  him  its 
applications  to  the  profession  that  he  has  chosen. 
Dr.  Draper,  as  an  old  teacher,  knew  well  the  diffi- 
culties to  be  encountered  in  bringing  his  subject 


While  all  enlightened  physicians  will  agree  that 
ics  is  desirable  for  the  medi- 


cal student,  only  those  actually  engaged  in  the 
teaching  of  the  primary  subjects  can  be  fully 
aware  of  the  difficulties  encountered  by  students 
who  attempt  the  study  of  these  subjects  without 
a,  knowledge  of  either  physics  or  chemistry. 
These  are  especially  felt  by  the  teacher  of  physi- 
ology. 

It  is,  however,  impossible  for  him  to  impart  a 
knowledge  of  the  main  facts  of  his  subject  and 
•establish  them  by  reasons  and  experimental  dem- 
onstration, and  at  the  same  time  undertake  to 
teach  nb  initio  the  principles  of  chemistry  or  phys- 
ics. Hence  the  desirability,  we  may  say  the 
necessity,  for  some  such  work  as  the  present  one. 


within  the  grasp  of  the  average  student,  and  that 
he  has  succeeded  so  well  proves  once  more  that 
the  man  to  write  for  and  examine  students  is  the 
one  who  has  taught  and  is  teaching  them.  The 
book  is  well  printed  and  fully  illustrated,  and  in 
every  way  deserves  grateful  recognition. — The 
Montreal  Medical  Journal,  July,  1890. 


j.  MCGREGOR,  m.  A.,  M. 

Muirhead  Demonstrator  of  Physiology,  University  of  Glasgow. 


Physiological  Physics.     In  one  12mo.  volume  of  537  pages,  with  219  illustra- 
j.     Limp  cloth,  $2.00.    See  Student  ~ 


tions. 

The  title  of  this  work  sufficiently  explains  the 
nature  of  its  contents.  It  is  designed  as  a  man- 
ual for  the  student  of  medicine,  an  auxiliary  to 
fais  text- book  in  physiology,  and  it  would  be  particu- 
larly useful  as  a  guide  to  his  laboratory  experi- 


Series  of  Manuals,  page  31. 

ments.  It  will  be  found  of  great  value  to  the 
practitioner.  It  is  a  carefully  prepared  book  of 
reference,  concise  and  accurate,  and  as  such  we 
heartily  recommend  it. — Journal  of  the  American 
Medical  Association,  Dec.  6. 1884. 


&  ALTON,  JOHN  €.,  M.  D., 

Professor  Emeritus  of  Physiology  in  the  College  of  Physicians  and  Surgeons,  New  York. 

Doctrines  of  the  Circulation  of  the  Blood.  A  History  of  Physiological 
Opinion  and  Discovery  in  regard  to  the  Circulation  of  the  Blood.  In  one  handsome 
I2mo.  volume  of  293  pages.  Cloth,  $2. 

revolutionized  the  theories  of  teachers,  than  the 
discovery  of  the  circulation  of  the  blood.  This 
explains  the  extraordinary  interest  it  has  to  all 


Dr.  Dal  ton's  work  is  the  fruit  of  the  deep  research 
of  a  cultured  mind,  and  to  the  busy  practitioner  it 
cannot  fail  to  be  a  source  of  instruction.  It  will 
inspire  him  with  a  feeling  of  gratitude  and  admir- 
ation for  those  plodding  workers  of  olden  times, 
who  laid  the  foundation  of  the  magnificent  temple 
of  medical  science  as  it  now  stands. — New  Orleans 
Medical  and  Surgical  Journal,  Aug.  1885. 

In  the  progress  of  physiological  study  no  fact 


medical  historians.  The  volume  before  us  is  one 
of  three  or  four  which  have  been  written  within  a 
few  years  by  American  physicians.  It  is  in  several 
respects  the  most  complete.  The  volume,  though 
small  in  size,  is  one  of  the  most  creditable  con- 
tributions from  an  American  pen  to  medical  history 


was  of  greater  moment,  none  more  completely  |  that  has  appeared. — Med.  <t  Surg.  Rep.,  Dec.  6, 1884. 


BELL,  F.  JEFFREY,  M.  A.9 

Professor  of  Comparative  Anatomy  at  King's  College,  London. 

Comparative  Physiology  and  Anatomy.  In  one  12mo.  volume  of  561  pages, 
with  229  illustrations.  Limp  cloth,  $2.00.    See  Students'  Series  of  Manuals,  page  31. 

The  manual  is  preeminently  a  student's  book — 
dear  and  simple  in  language  and  arrangement. 
It  is  well  and  abundantly  illustrated, 


s  read- 


able and  interesting.    On  the  whole  we  consider 


it  the  best  work   in   existence   in   the  English 


language  to  place  in  the  hands  of  the    medi< 
student.— Bristol  Medico-Chirurgical  Journal,  M 


medical 
!ar. 


ELLIS,  GEORGE  VINER, 

Emeritus  Professor  of  Anatomy  in  University  College,  London. 

Demonstrations  of  Anatomy.  Being  a  Guide  to  the  Knowledge  of  the 
Human  Body  by  Dissection.  From  the  eighth  and  revised  London  edition.  In  one  very 
handsome  octavo  volume  of  716  pages,  with  249  illustrations.  Cloth,  $4.25 ;  leather,  $5.25. 

ROBERTS,  JOHN  B.,  A.  M.9  M.  D., 

Lecturer  in  Anatomy  in  the  University  of  Pennsylvania. 

The  Compend  of  Anatomy.  For  use  in  the  dissecting-room  and  in  preparing 
for  examinations.  In  one  16mo.  volume  of  196  pages.  Limp  cloth,  75  cents. 


8        LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Physiology,  Chemistry. 


CHAPMAN,  HENRY  €.,  M.  D., 

Professor  of  Institutes  of  Medicine  and  Medical  Juris,  in  the  Jefferson  Med,  Coll.  of  Philadelphia* 

A  Treatise  on   Human  Physiology.     In  one  handsome  octavo  volume  of 
925  pages,  with  605  fine  engravings.     Cloth,  $5.50  ;  leather,  $6.50. 


It  represents  very  fully  the  existing  state  of 
physiology.  The  present  work  has  a  special  value 
to  the  student  and  practitioner  as  devoted  more 
to  the  practical  application  of  well-known  truths 
which  the  advance  of  science  has  given  to  the 
profession  in  this  department,  which  may  be  con- 
sidered the  foundation  of  rational  medicine.— Buf- 
falo Medical  and  Surgical  Journal,  Dec.  1887. 

Matters  which  have  a  practical  bearing  on  the 
practice  of  medicine  are  lucidly  expressed;  tech- 
nical matters  are  given  in  minute  detail;  elabo- 
rate directions  are  stated  for  the  guidance  of  stu- 
dents in  the  laboratory.  In  every  respect  the 
work  fulfils  its  promise,  whether  as  a  complete 
treatise  for  the  student  or  for  the  physician  ;  for 
the  former  it  is  so  complete  that  he  need  look  no 


farther,  and  the  latter  will  find  entertainment  and 
instruction  in  an  admirable  book  of  reference. — 
North  Carolina  Medical  Journal,  Nov.  1887. 

The  work  certainly  commends  itself  to  both 
student  and  practitioner.  What  is  most  demanded 
by  the  progressive  physician  of  to-day  is  an  adap- 
tation of  physiology  to  practical  therapeutics,  and 
this  work  is  a  decided  improvement  in  this  respect 
over  other  works  in  the  market.  It  will  certainly 
take  place  among  the  most  valuable  text-books.— 
Medical  Age,  Nov.  25, 1887. 

It  is  the  production  of  an  author  delighted  with 
his  work,  and  able  to  inspire  students  with  an  en- 
thusiasm akin  to  his  own.— American  Practitioner 
and  News,  Nov.  12, 1887. 


&  ALTON,  JOHN  €.,  M.  1)., 

Professor  of  Physiology  in  the  College  of  Physicians  and  Surgeons,  New  York,  etc. 

A  Treatise  on  Human  Physiology.  Designed  for  the  use  of  Students  and 
Practitioners  of  Medicine.  Seventh  edition,  thoroughly  revised  and  rewritten.  In  one 
very  handsome  octavo  volume  of  722  pages,  with  252  beautiful  engravings  on  wood.  Cloth. 
$5.00;  leather,  $6.00. 

From  the  first  appearance  of  the  book  it  has 
been  a  favorite,  owing  as  well  to  the  author's 
renown  as  an  oral  teacher  as  to  the  charm  of 
simplicity  with  which,  as  a  writer,  he  always 
succeeds  in  investing  even  intricate  subjects. 
It  must  be  gratifying  to  him  to  observe  the  fre- 


quency with  which  his  work,  written  for  students 
and  practitioners,  is  quoted  by  other  writers  on 
physiology.  This  fact  attests  its  value,  and,  in 
great  measure,  its  originality.  It  now  needs  no 
such  seal  of  approbation,  however,  for  the  thou- 
sands who  have  studied  it  in  its  various  editions 


have  never  been  in  any  doubt  as  to  its  sterling- 
worth.—^.  Y.  Medical  Journal,  Oct.  1882. 

Professor  Dalton's  well-known  and  deservedly- 
appreciated  work  has  long  passed  the  stage  at 
which  it  could  be  reviewed  in  the  ordinary  sense. 
The  work  is  eminently  one  for  the  medical  prac- 
titioner, since  it  treats  most  fully  of  those  branches 


VAUftWUVA.   O-ILIV^    XU   Ul^Ctl/O  illlTDK  1UI1JT    VI    tUVO*?    UlttlUJilC.^ 

of  physiology  which  have  a  direct  bearing  on  the 
diagnosis  and  treatment  of  disease.  The  work  is 
one  which  we  can  highly  recommend  to  all  our 
readers.— Dublin  Journal  of  Medical  Science,  Feb.'83_ 


FOSTER,  MICHAEL,  M.  D.,  F.  R.  S., 

Prelector  in  Physiology  and  Fellow  of  Trinity  College,  Cambridge,  England. 
Text-Book  of  Physiology.     New  (fourth)  and  enlarged  American  from  the 
fifth  and  revised  English  edition,  with  notes  and  additions.     Preparing. 

A   REVIEW  OF    THE  FIFTH   ENGLISH   EDITION   IS  APPENDED. 

It  is  delightful  to  meet  a  book  which  deserves 
only  unqualified  praise.  Such  a  book  is  now  before 
us.  It  is  in  all  respects  an  ideal  text-book.  With  a 
complete,  accurate  and  detailed  knowledge  of  his 
subject,  the  author  has  succeeded  in  giving  a 
thoroughly  consecutive  and  philosophic  account 
of  the  science.  A  student's  attention  is  kept 
throughout  fixed  on  the  great  and  salient  ques- 


tions, and  his  energies  are  not  frittered  away  and 
degenerated  on  petty  and  trivial  details.  Review- 
ing this  volume  as  a  whole  we  are  justified  in  say- 
ing that  it  is  the  only  thoroughly  good  text-book 
of  physiology  in  the  English  language,  and  that  il 
is  jarobably  the  best  text-book  in  any  language, 
—Edinburgh  Medical  Journal,  December  1889. 


POWER,  HENRY,  M.  B.,  F.  R.  C.  8., 

Examiner  in  Physiology,  Royal  College  of  Surgeons  of  England. 

Human  Physiology.  Second  edition.  In  one  handsome  pocket-size  12mo.  vol- 
ume of  509  pp.,  with  68  illustrations.  Cloth,  $1.50.  See  Students'  Series  of  Manuals,  p.  31. 

SIMON,  W.,  PJi.  Z>.,  M.  &., 

Professor  of  Chemistry  and  Toxicology  in  the  College  of  Physicians  and  Surgeons,  Baltimore,  and 
Professor  of  Chemistry  in  the  Maryland  College  of  Pharmacy. 

Manual  Of  Chemistry.  A  Guide  to  Lectures  and  Laboratory  work  for  Beginners 
in  Chemistry.  A  Text-book,  specially  adapted  for  Students  of  Pharmacy  and  Medicine. 
New  (second)  edition.  In  one  8vo.  vol.  of  478  pp.,  with  44  woodcuts  and  7  colored  plates 
illustrating  56  of  the  most  important  chemical  tests.  Cloth,  $3.25. 


In  this  book  the  author  has  endeavored  to  meet 
the  wants  of  the  student  of  medicine  or  pharmacy 
in  regard  to  his  chemical  studies,  and  he  has  suc- 
ceeded in  presenting  his  subject  so  clearly  that  no 
one  who  really  wishes  to  acquire  a  fair  knowledge 
of  chemistry  can  fail  to  do  so  with  the  help  of  this 
work.  The  largest  section  of  the  book  is  naturally 
that  devoted  to  the  consideration  of  the  carbon 
compounds,  or  organic  chemistry.  An  excellent 


feature  is  the  introduction  of  a  number  of  plates 
showing  the  various  colors  of  the  most  important 
chemical  reactions  of  the  metallic  salts,  of  some 
of  the  alkaloids,  and  of  the  urinary  tests.  In  the 
part  treating  of  physiological  chemistry  the  section 
on  analysis  of  the  urine  will  be  found  very  practi- 
cal, and  well  suited  to  the  needs  of  the  practitioner 
of  medicine.—  The  Medical  Record,  May  25, 1889. 


Wohler's  Outlines  of  Organic  Chemistry.    Edited  by  FITTTG.    Translated 
by  IRA  EEMSEN,  M.  D.,  Ph.  D.    In  one  12mo.  volume  of  550  pages.    Cloth,  $3. 


LEHMANN'S  MANUAL  OF  CHEMICAL  PHYS- 
IOLOGY. In  one  octavo  volume  of  327  pages, 
with  41  illustrations.  Cloth,  $2.26. 

CARPENTER'S  HUMAN  PHYSIOLOGY.  Edited 
by  HENKT  POWEB.  In  one  octavo  volume. 


CARPENTER'S  PRIZE  ESSAY  ON  THE  USE  AND 
ABUSE  OF  ALCOHOLIC  LIQUOBS  IN  HEALTH  AND  Dis- 
EASE.  With  explanations  of  scientific  words.  Small 
12mo.  178  pages.  Cloth,  60  cents. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Chemistry. 


FRANKLANI>9E.,I>.  C.L.,F.R.S.,&JAPP,  F.R.,F.I.  C.9 

Assist.  Prof,  of  Chemistry  in  the  Normal 
School  of  Science,  London. 


Professor  of  Chemistry  in  the  Normal  School 
of  Science,  London. 

Inorganic  Chemistry.     In  one  handsome  octavo  volume  of  677  pages  with  51 
woodcuts  and  2  plates.     Cloth,  $3.75  ;  leather,  $4.75. 

This  excellent  treatise  will  not  fail  to  take  its 


place  as  one  of  the  very  best  on  the  subject  of 
which  it  treats.  We  have  been  much  pleased 
with  the  comprehensive  and  lucid  manner  in 


which  the 


omp 
diffi 


culties  of  chemical  notation  and 


This  work  should  supersede  other  works  of  its 
class  in  the  medical  colleges.  It  is  certainly  better 
adapted  than  any  work  upon  chemistry.with  which 
we  are  acquainted,  to  impart  that  clear  and  full 
knowledge  of  the  science  which  students  of  med- 
icine should  have.  Physicians  who  feel  that  their 
chemical  knowledge  is  behind  the  times,  would 
do  well  to  devote  some  of  their  leisure  time  to  the 
study  of  this  work.  The  descriptions  and  demon- 
strations are  made  so  plain  that  there  is  no  diffi- 
culty in  understanding  them. — Cincinnati  Medical 
News,  January,  1886. 

FOWNES,  GEORGE,  Ph.  D. 

A  Manual  of  Elementary  Chemistry;  Theoretical  and  Practical.  Em- 
bodying WATTS'  Physical  and  Inorganic  Chemistry.  New  American,  from  the  twelfth  English 
edition.  In  one  large  royal  12mo.  volume  of  1061  pages,  with  168  illustrations  on  wood 
and  a  colored  plate.  Cloth,  $2.75 ;  leather,  $3.25. 


nomenclature  have  been  cleared  up  by  the  writers. 
It  shows  on  every  page  that  the  problem  of 
rendering  the  obscurities  of  this  science  easy 
of  comprehension  has  long  and  successfully 
engaged  the  attention  of  the  authors.—  Medical 
and  Surgical  Reporter,  October  31,  1885. 


Fownes*  Chemistry  has  been  a  standard  text- 
book upon  chemistry  for  many  years.  Its  merits 
are  very  fully  known  by  chemists  and  physicians 
everywhere  in  this  country  and  in  England.  As 
the  science  has  advanced  by  the  making  of  new 
•discoveries,  the  work  has  been  revised  so  as  to 
keep  it  abreast  of  the  times.  It  has  steadily 
maintained  its  position  as  a  text-book  with  medi- 
cal students.  In  this  work  are  treated  fully :  Heat, 
Light  and  Electricity,  including  Magnetism.  The 
influence  exerted  by  these  forces  in  chemical 
action  upon  health  and  disease,  etc.,  is  of  the  most 
important  kind,  and  should  be  familiar  to  every 
medical  practitioner.  We  can  commend  the 


work  as  one  of  the   very  best  text-books    upon 
chemistry  extant.— Cincinnati  Med.  News,  Oct.  '85. 
Of  all  the  works  on  chemistry  intended  for  the 
use  of  medical    students,  Fownes'  Chemistry   is 


perhaps  the  most  widely  used. 

based  upon  its  excellence.    This  last  edition  con 


Its  popularity  is 

upon  its  excellence.    This  last  editi 
tains  all  of  the  material  found  in  the  previous, 

xx  ««^;«i,^^i   u».  *v«  «,i,i;^;^«  ~*  TIT-H,,? 


and  it  is  also  enriched  by  the  addition  of  Watts 
Physical  and  Inorganic  Chemistry.  All  of  the  mat- 
ter is  brought  to  the  present  standpoint  of  chemi- 
cal knowledge.  We  may  safely  predict  for  this 
work  a  continuance  of  the  fame  and  favor  it  enjoys 
among  medical  students.— New  Orleans  Medical 
and  Surgical  Journal,  March,  1886. 


ATTFIELD,  JOHN,  M.  A.,  Ph.  D.9  F.  I.  C.,  F.  R.  8.,  Etc. 

Professor  of  Practical  Chemistry  to  the  Pharmaceutical  Society  of  Great  Britain,  etc. 

Chemistry,  General,  Medical  and  Pharmaceutical;  Including  the  Chem- 
istry of  the  U.  S.  Pharmacopeia.  A  Manual  of  the  General  Principles  of  the  Science, 
and  their  Application  to  Medicine  and  Pharmacy.  A  new  American,  from  the  twelfth 
English  edition,  specially  revised  by  the  Author  for  America.  In  one  handsome  royal 
12mo.  volume  of  782  pages,  with  88  illustrations.  Cloth,  $2.75;  leather,  $3.25. 

again  it  is  a  good  laboratory  guide,  and  finally  it 
contains  such  a  mass  of  well-arranged  information 
that  it  will  always  serve  as  a  handy  book  of  refer- 
ence. He  does  not  allow  any  unutilizable  knowl- 
edge to  slip  into  his  book;  his  long  years  of 
experience  have  produced  a  work  which  is  both 
scientific  and  practical,  and  which  shuts  out 
everything  in  the  nature  of  a  superfluity,  and 
therein  lies  the  secret  of  its  success.  This  last 
edition  shows  the  marks  of  the  latest  progress 
made  in  chemistry  and  chemical  teaching.— Nevi 
Orleans  Medical  and  Surgical  Journal,  Nov.  1889. 


Attfield's  Chemistry  is  the  most  popular  book 
among  students  of  medicine  and  phai  macy.  This 
popularity  has  a  good,  substantial  basis.  It  rests 
upon  real  merits.  Attneld's  work  combines  in  the 
happiest  manner  a  clear  exposition  of  the  theory 
of  cnemislry  with  the  practical  application  of  this 
knowledge  to  the  everyday  dealings  of  the  phy- 
sician and  pharmacist.  His  discernment  is  shown 
not  only  in  what  he  puts  into  his  work,  but  also  in 
what  he  leaves  out.  His  book  is  precisely  what 
the  title  claims  for  it.  The  admirable  arrangement 
of  the  text  enables  a  reader  to  get  a  good  idea  of 
chemistry  without  the  aid  of  experiments,  and 


BLOXAM,  CHARLES  L., 

Professor  of  Chemistry  in  King's  College,  London. 

Chemistry,  Inorganic  and  Organic.  New  American  from  the  fifth  Lon- 
don edition,  thoroughly  revised  and  much  improved.  In  one  very  handsome  octavo 
volume  of  727  pages,  with  292  illustrations.  Cloth,  $2.00 ;  leather,  $3.00. 


Comment  from  us  on  this  standard  work  is  al- 
most superfluous.  It  differs  widely  in  scope  and 
aim  from  that  of  Attfield,  and  in  its  way  is  equally 
beyond  criticism.  It  adopts  the  most  direct  meth- 
ods in  stating  the  principles,  hypotheses  and  facts 
of  the  science.  Its  language  is  so  terse  and  lucid, 
and  its  arrangement  of  matter  so  logical  in  se- 
quence that  the  student  never  has  occasion  to 
complain  that  chemistry  is  a  hard  study.  Much 
attention  is  paid  to  experimental  illustrations  of 
chemical  principles  and  phenomena,  and  the 
mode  of  conducting  these  experiments.  The  book 
maintains  the  position  it  has  always  held  as  one  of 


the  best  manuals  of  general  chemistry  m  the  Eng- 
lish language.— Detroit  Lancet,  Feb.  1884. 

We  know  of  no  treatise  on  chemistry  which 
contains  so  much  practical  information  in  the 
same  number  of  pages.  The  book  can  be  readily 
adapted  not  only  to  the  needs  of  those  who  desire 
a  tolerably  complete  course  of  chemistry,  but  also 
to  the  needs  of  those  who  desire  only  a  general 
knowledge  of  the  subject.  We  take  pleasure  in 
recommending  this  work  both  as  a  satisfactory 
text- book,  and  as  a  useful  book  of  reference.— .Bos- 
ton Medical  and  Surgical  Journal,  June  19, 1884. 


WILLIAM  H.,  M.  D., 

Demonstrator  of  Chemistry  in  the  Medical  Department  of  the  University  of  Pennsylvania. 

A  Manual  of  Medical  Chemistry.  For  the  use  of  Students.  Based  upon  Bow- 
man's Medical  Chemistry.  In  one  12mo.  volume  of  310  pages,  with  74  illus.  Cloth,  $1.75. 
It  is  a  concise  manual  of  three  hundred  pages,  the  recognition  of  compounds  due  to  pathological 
giving  an  excellent  summary  of  the  best  methods  conditions.  The  detection  of  poisons  is  treated 
of  analyzing  the  liquids  and  solids  of  the  body,  both  with  sufficient  fulness  for  the  purpose  of  the  stu- 
for  the  estimation  of  their  normal  constituent  and  dent  or  practitioner.— Boston  Jl.  of  Chem.  June,  '80. 


10 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Chemistry. 


REMSEN,  IRA,  M.  !>.,  Ph.  D., 

Professor  of  Chemistry  in  the  Johns  Hopkins  University,  Baltimore' 

Principles  of  Theoretical  Chemistry,  with  special  reference  to  the  Constitu- 
tion of  Chemical  Compounds.  New  (third)  and  thoroughly  revised  edition.  In  one  hand- 
some royal  12mo.  volume  of  316  pages.  Cloth,  $2.00 

This  work  of  Dr.  Remsen  is  the  very  text-book 
needed,  and  the  medical  student  who  has  it  at 
his  fingers'  ends,  so  to  speak,  can,  if  he  chooses, 
make  Himself  familiar  with  any  branch  of  chem- 
istry which  he  may  desire  to  pursue.  It  would  be 
difficult  indeed  to  find  a  more  lucid,  full,  and  at 
the  same  time  compact  explication  of  the  philos- 


ophy of  chemistry,  than  the  book  before  us,  and 
we  recommend  it  to  the  careful  and  impartial 


examination  of  college  faculties  as  the  text-book  of 
chemical  instruction.—^.  Louis  Medical  and  Sur- 
gical Journal,  January,  1888. 

It  is  a  healthful  sign  when  we  see  a  demand  for 
a  third  edition  of  such  a  book  as  this.    This  edi- 
tion is  larger  than  the  last  by  about  seventy -five 
and  much  of  it  has  been  rewritten,  thus 


pages,  and  much  of  it  has  been  rewritten,  thus 
bringing  it  fully  abreast  of  the  latest  investiga- 
tions.—N.  Y.  Medical  Journal,  Dec.  31, 1887. 


CHARLES,  T.  CRANSTOTJN,  M.  D.,  F.  €.  S.,  M.  S., 

Formerly  Asst.  Prof,  and  Demonst.  of  Chemistry  and  Chemical  Physics,  Queen's  College,  Belfast. 

The  Elements  of  Physiological  and  Pathological  Chemistry.     A 

Handbook  for  Medical  Students  and  Practitioners.  Containing  a  general  account  of 
Nutrition,  Foods  and  Digestion,  and  the  Chemistry  of  the  Tissues,  Organs,  Secretions  and 
Excretions  of  the  Body  in  Health  and  in  Disease.  Together  with  the  methods  for  pre- 
paring or  separating  their  chief  constituents,  as  also  for  their  examination  in  detail,  and 
an  outline  syllabus  of  a  practical  course  of  instruction  for  students.  In  one  handsome  octave- 
volume  of  463  pages,  with  38  woodcuts  and  1  colored  plate.  Cloth,  $3.50. 


Dr.  Charles  is  fully  impressed  with  the  impor- 
tance and  practical  reacn  of  his  subject,  and  he 
has  treated  it  in  a  competent  and  instructive  man- 
ner. We  cannot  recommend  a  better  book  than 
the  present.  In  fact,  it  fills  a  gap  in  medical  text- 
books, and  that  is  a  thing  which  can  rarely  be  said 


nowadays.  Dr.  Charles  has  devoted  much  space 
to  the  elucidation  of  urinary  mysteries.  He  does 
this  with  much  detail,  and  yet  in  a  practical  and 
intelligible  manner.  In  fact,  the  author  has  filled 
his  book  with  many  practical  hints. — Medical  Rec- 
ord, December  20, 1884. 


HOFFMANN,  F.,  A.M.,  Ph.D.,  &  POWER,  F.B.,  Ph.D., 

Public  Analyst  to  the  State  of  New  York.  Prof,  of  Anal.  Chem.  in  the  Phil.  Coll.  of  Pharmacy. 

A  Manual  of  Chemical  Analysis,  as  applied  to  the  Examination  of  Medicinal 
Chemicals  and  their  Preparations.  Being  a  Guide  for  the  Determination  of  their  Identity 
and  Quality,  and  for  the  Detection  of  Impurities  and  Adulterations.  For  the  use  of 
Pharmacists,  Physicians,  Druggists  and  Manufacturing  Chemists,  and  Pharmaceutical  and 
Medical  Students.  Third  edition,  entirely  rewritten  and  much  enlarged.  In  one  very 
handsome  octavo  volume  of  621  pages,  with  179  illustrations.  Cloth,  $4.25. 

tion  of  them  singularly  explicit.  Moreover,  it  i& 
exceptionally  free  from  typographical  errors.  We 
have  no  hesitation  in  recommending  it  to  those 
who  are  engaged  either  in  the  manufacture  or  the 
testing  of  medicinal  chemicals.— .London  Pharma- 
ceutical Journal  and  Transactions,  1883. 


We  congratulate  the  author  on  the  appearance 
of  the  third  edition  of  this  work,  published  for  the 


first  time  in  this  country  also. 


is  admirable  and 


the  information  it  undertakes  to  supply  is  both 
extensive  and  trustworthy.  The  selection  of  pro- 
cesses for  determining  the  purity  of  the  substan- 
ces of  which  it  treats  Is  excellent  and  the  descrip- 


CLOWES,  FRANK,  D.  Sc.,  London, 

Senior  Science- Master  at  the  High  School,  Newcastle-under-Lyme,  etc. 

An  Elementary  Treatise  on  Practical  Chemistry  and  Qualitative 
Inorganic  Analysis.  Specially  adapted  for  use  in  the  Laboratories  of  Schools  and 
Colleges  and  by  Beginners.  Third  American  from  the  fourth  and  revised  English  edition. 
In  one  very  handsome  royal  12mo.  volume  of  387  pages,  with  55  illustrations.  Cloth, 
$2.50. 

student  in   the   performance  of  each   analysis. 

These  characteristic! 


This  work  has  long  been  a  favorite  with  labora- 
tory instructors  on  account  of  its  systematic  plan, 
carrying  the  student  step  by  step  from  the  simplest 
questions  of  chemical  analysis,  to  the  more  recon- 
dite problems.  Features  quite  as  commendable 
are  the  regularity  and  system  demanded  of  the 


ics  are  preserved  in  the  present 
edition,  which  we  can  heartily  recommend  as  a  sat- 
isfactory guide  for  the  student  of  inorganic  chem- 
ical analysis. — New  York  Medical  Journal,  Oct.  9, 
1886. 


RALFE,  CHARLES  H.,  M.  D.,  F.  R.  C.  P., 

Assistant  Physician  at  the  London  Hospital. 

Clinical  Chemistry.    In  one  pocket-size  12mo.  volume  of  314  pages,  with  16 

See  Students'  Series  of  Manuals,  page  31. 
cine.  Dr.  Ralfe  is  thoroughly  acquainted  with  the 
latest  contributions  to  his  science,  and  it  is  quite 
refreshing  to  find  the  subject  dealt  with  so  clearly 
and  simply,  yet  in  such  evident  harmony  with  the 
modern  scientific  methods  and  spirit.— Medical 
Record,  February  2, 1884. 


illustrations.    Limp  cloth,  red  edges,  $1.50. 

This  is  one  of  the  most  instructive  little  works 

that  we  have  met  with  in  a  long  time.   The  author 

"1  as  a  ch 

>rac- 
tto 
know,  of  tlTe  applications  of  chemistry  in  medi- 


CLASSEN,  ALEXANDER, 

Professor  in  the  Royal  Polytechnic  School,  Aix-la-Chapelle. 

Elementary  Quantitative  Analysis.  Translated,  with  notes  and  additions,  by 
EDGAR  F.  SMITH,  Ph.  D.,  Assistant  Professor  of  Chemistry  in  the  Towne  Scientific  School, 
University  of  Penna.  In  one  12mo.  volume  of  324  pages,  with  36  illus.  Cloth,  $2.00. 

and  then  advancing  to  the  analysis  of  minerals  and 


It  is  probably  the  best  manual  of  an  elementary 
nature  extant,  insomuch  as  its  methods  are  the 
best.  It  teaches  by  examples,  commencing  with 
single  determinations,  followed  by  separations, 


such  products  as  are  met  with  in  applied  chemis- 
try. It  is  an  indispensable  book  for  students  in 
chemistry.— .Boston  Journal  of  Chemistry,  Oct.  1878. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Pharm.,  Mat.  Med.,  Therap.  11 


HARE,  HOB  ART  AMORY,  B.  Sc.,  M.  D., 

Clinical  Professor  of  Diseases  of  Children  and  Demonstrator  of  Therapeutics  in  the  University  of 
Pennsylvania;  Secretary  of  the  Convention  for  the  Revision  of  the  United  States  Pharmacopoeia  of 
1890. 

A  Text-Book  of  Practical  Therapeutics ;  With  Especial  Reference  to  the 
Application  of  Kemedial  Measures  to  Disease  and  their  Employment  upon  a  Rational 
Basis.  With  special  chapters  by  DRS.  G.  E.  DE  SCHWEINITZ,  EDWARD  MARTIN, 
J.  HOWARD  REEVES  and  BARTON  C.  HIRST.  In  one  handsome  octavo  volume  of  622 
Cloth,  $3.75;  leather,  $4.75. 

ent  volume  is  in  many  respects  unique  and  a  great 
credit  to  the  author.  Dr.  Hare  is  already  well 
known  as  an  able  experimental,  didactic  and 
clinical  therapeutist,  a  happy  combination,  which 
has  eminently  fitted  him  for  the  preparation  of  the 
present  work.  He  is  thoroughly  acquainted  with 
the  latest  contributions  to  therapeutical  science, 
and  his  book  represents  the  actual  state  of  the 
science.  It  is  a  model  of  concise,  clear  and  forci- 
ble description,  an  exponent  of  plain  facts,  and  a 
thoroughly  practical  guide  to  the  rational  treat- 
ment of  disease.  Books  like  this  make  a  lasting 
impression.  We  heartily  commend  the  present 
volume  to  the  student,  the  scientific  therapeutist 
and  the  general  practitioner,  not  only  as  a  most 
satisfactory  text-book,  but  also  as  a  highly  valua- 
ble work  of  reference.  We  bespeak  for  Dr.  Hare's 
"  Practical  Therapeutics  "  the  greatest  success  in 
every  way.--  University  Medical  Magazine,  Nov.  1890. 


pages. 

That  the  student  is  too  often  required  to  perform 
acrobatic  feats  of  memory  and  invention  in  asso- 
ciating and  reconciling  widely  separated  state- 
ments is  certain,  and  disgust  over  his  failure  is 
apt  to  develop  him  into  a  physician,  without  faith 
in  the  reasonableness  of  his  art.  Dr.  Hare  has 
obviated  this  difficulty  by  comprising  in  one 
cover  a  work  on  therapeutics  and  on  treatment, 
each  part  being  so  interwoven  with  the  other  by 
references  that  there  will  be  the  least  possible  diffi- 
culty in  learning  and  remembering  the  nature  of 
therapeutic  resource?,  and  in  using  them  to  the 
best  advantage.  The  portion  devoted  to  treat- 
ment occupies  at  least  one-half  of  the  work,  with 
clear  directions  for  the  therapeutic  measures  to 
be  employed,  together  with  the  reasons  for  the 
choice  of  drugs,  according  to  the  varying  stages 
and  symptoms.— Medical  Age,  September  25, 1890. 

We  may  say  without  exaggeration  that  the  pres- 


BRUNTON, T.  LAUDER,  M.D.,  D.Sc.,  F.R.S.,  F.R.C.P., 

Lecturer  on  Materia  Medica  and  Therapeutics  at  St.  Bartholomew's  Hospital,  London,  etc. 

A  Text-Book  of  Pharmacology,  Therapeutics  and  Materia  Medica ; 

Including  the  Pharmacy,  the  Physiological  Action  and  the  Therapeutical  Uses  of  Drugs. 
Third  edition.    Octavo,  1305  pages,  230  illustrations.    Cloth,  $5.50 ;  leather,  $6.50. 

No  words  of  praise  are  needed  for  this  work,  for 
it  has  already  spoken  for  itself  in  former  editions. 
It  was  by  unanimous  consent  placed  among  the 
foremost  oooks  on  the  subject  ever  published  in 
any  language,  and  the  better  it  is  known  and  studied 
the  more  highly  it  is  appreciated.  The  present 
•edition  contains  much  new  matter,  the  insertion 
of  which  has  been  necessitated  by  the  advances 


made  in  various  directions  in  the  art  of  therapeu- 
tics, and  it  now  stands  unrivalled  in  its  thoroughly 
scientific  presentation  of  the  modes  of  drug  action. 
No  one  who  wishes  to  be  fully  up  to  the  times  in 
this  science  can  afford  to  neglect  the  study  of  Dr. 
Brunton's  work.  The  indexes  are  excellent,  and 
add  not  a  little  to  the  practical  value  of  the  book. 
—Medical  Record,  May  25, 1889. 


MAISCH,  JOSLNM.,  Phar.  D., 

Professor  of  Materia  Medica  and  Botany  in  the  Philadelphia  College  of  Pharmacy. 

A  Manual  of  Organic  Materia  Medica;  Being  a  Guide  to  Materia  Medica  of 
the  Vegetable  and  Animal  Kingdoms.  For  the  use  of  Students,  Druggists,  Pharmacists 
and  Physicians.  New  (4th)  edition,  thoroughly  revised.  In  one  handsome  royal  12mo. 
volume  of  529  pages,  with  258  illustrations.  Cloth,  $3. 

fore  his  eyes.  That  it  answers  its  purposes  in  this 
respect  the  rapid  succession  of  editions  is  the  best 
evidence.  It  is  the  favorite  book  of  the  American 
student  even  outside  of  Maisch's  several  hundred 


For  everyone  interested  in  materia  medica, 
Maisch's  Manual,  first  published  in  1882,  and  now 
in  its  fourth  edition,  is  an  indispensable  book. 
For  the  American  pharmaceutical  student  it  is 
the  work  which  will  give  him  the  necessary  knowl- 
edge in  the  easiest  way,  partly  because  the  text  is 
brief,  concise,  and  free  from  unnecessary  matter, 
and  partly  because  of  the  numerous  illustrations, 
which  bring  facts  worth  knowing  immediately  be- 


personal  students.  The  arrangement  of  its  con- 
tents shows  the  practical  tendency  of  the  book. 
Maisch's  system  of  classification  is  easy  and  eom- 

Srehensive.— Pharmaceutische   Zeitung,   Germany, 
390. 


PARRISH,  EDWARD, 

Late  Professor  of  the  Theory  and  Practice  of  Pharmacy  in  the  Philadelphia  College  of  Pharmacy. 
A  Treatise  on  Pharmacy :    Designed  as  a  Text-book  for  the  Student,  and  as  a 
Guide  for  the  Physician  and  Pharmaceutist.    With  many  Formulae  and  Prescriptions. 
Fifth  edition,  thoroughly  revised,  by  THOMAS  S.  WIEGAND,  Ph.  G.     In  one  handsome 
octavo  volume  of  1093  pages,  with  256  illustrations.    Cloth,  $5 ;  leather,  $6. 

No  thorough-going  pharmacist  will  fail  to  possess  |  ods  of  combination  are  concerned,  can  afford  to 
himself  of  so  useful  a  guide  to  practice,  and  no  j  leave  this  work  out  of  the  list  of  their  works  of 

reference.  The  country  practitioner,  who  must 
always  be  in  a  measure  his  own  pharmacist,  will 
find  it  indispensable.— Louisville  Medical  News, 


guiu.c?    \i\j  puvjLUJc;,    nun    uv 

physician  who  properly  estimates  the  value  of  an 
accurate  knowledge  of  the  remedial  agents  em- 
ployed by  him  in  daily  practice,  so  far  as  their 
miscibility,  compatibility  and  most  effective  meth- 


March  29, 1884. 


HERMANN,  Dr.  L., 

Professor  of  Physiology  in  the  University  of  Zurich. 

Experimental  Pharmacology.  A  Handbook  of  Methods  for  Determining  the 
Physiological  Actions  of  Drugs.  Translated,  with  the  Author's  permission,  and  with 
•extensive  additions,  by  ROBERT  MEADE  SMITH,  M.  D.,  Demonstrator  of  Physiology  in  the 
University  of  Pennsylvania.  12mo.,  199  pages,  with  32  illustrations  Cloth,  $1.51 

STILLE,  ALFRED,  M.  D.,  LL.  D., 

Professor  of  Theory  and  Practice  of  Med.  and  of  Clinical  Med.  in  the  Univ.  of  Penna. 

Therapeutics  and  Materia  Medica.  A  Systematic  Treatise  on  the  Action  and 
Uses  of  Medicinal  Agents,  including  their  Description  and  History.  Fourth  edition, 
revised  and  enlarged.  In  two  large  and  handsome  octavo  volumes,  containing  1936  pages. 
Cloth,  $10.00;  leather,  $12.00. 


12        LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Mat.  Med.,  Therap. 


STILLE,  A.,  M.  D.,  LL.  D.,  &  MAISCH,  J.  M.,  Phar.  D., 


Professor  Emeritus  of  the  Theory  and  Prac- 
tice of  Medicine  and  of  Clinical  Medicine 
in  the  University  of  Pennsylvania. 


Prof,  of  Mat.  Med.  and  Botany  in  Phila. 
College  of  Pharmacy,  Sec* y  to  the  Ameri 
can  Pharmaceutical  Association. 


The  National  Dispensatory. 

CONTAINING  THENATURAL  HISTORY,  CHEMISTRY,  PHARMACY,  ACTIONS  AND   USES  OF 

MEDICINES,  INCLUDING  THOSE  RECOGNIZED  IN  THE  PHARMACOPEIAS  OF  THE 

UNITED  STATES,  GREAT  BRITAIN  AND  GERMANY,  WITH  NUMEROUS 

REFERENCES   TO  THE  FRENCH  CODEX. 

Fourth  edition  revised,  and  covering  the  new  British  Pharmacopoeia.  In  one  mag- 
nificent imperial  octavo  volume  of  1794  pages,  with  311  elaborate  engravings.  Price 
in  cloth,  $7.25  ;  leather,  raised  bands,  $8.00.  \*This  work  will  be  furnished  with  Patent 
Ready  Reference  Thumb-letter  Index  for  $1.00  in  addition  to  the  price  in  any  style  of  binding. 

In  this  new  edition  of  THE  NATIONAL  DISPENSATORY,  all  important  changes  in  the 
recent  British  Pharmacopoeia  have  been  incorporated  throughout  the  volume,  while  in 
the  Addenda  will  be  found,  grouped  in  a  convenient  section  of  24  pages,  all  therapeutical 
novelties  which  have  been  established  in  professional  favor  since  the  publication  of  the 
third  edition  two  years  ago.  Since  its  first  publication,  THE  NATIONAL  DISPENSATORY 
has  been  the  most  accurate  work  of  its  kind,  and  in  this  edition,  as  always  before,  it  may 
be  said  to  be  the  representative  of  the  most  recent  state  of  American,  English,  German 
and  French  Pharmacology,  Therapeutics  and  Materia  Medica. 
It  is  with  much  pleasure  that  the  fourth  edition  I  discovery  have  received  due  attention.— Kansas 


of  this  magnificent  work  is  received.  The  authors 
and  publishers  have  reason  to  feel  proud  of  this, 
the  most  comprehensive,  elaborate  and  accurate 
work  of  the  kind  ever  printed  in  this  country.  It 
is  no  wonder  that  it  has  become  the  standard  au- 
thority for  both  the  medical  and  pharmaceutical 
profession,  and  that  four  editions  have  been  re- 
quired to  supply  the  constant  and  increasing 
demand  since  its  first  appearance  in  1879.  The 
entire  field  has  been  gone  over  and  the  various 
articles  revised  in  accordance  with  the  latest 
developments  regarding  the  attributes  and  thera- 
peutical action  of  drugs.  The  remedies  of  recent 


City  Medical  Index,  Nov.  1887. 

We  think  it  a  matter  for  congratulation  that  the 
profession  of  medicine  and  that  of  pharmacy  have 
shown  such  appreciation  of  this  great  work  as  to  call 
for  four  editions  within  the  comparatively  brief 
period  of  eight  years.  The  matters  with  which  it 
deals  are  of  so  practical  a  nature  that  neither  the 
physician  nor  the  pharmacist  can  do  without  the 
latest  text- books  on  them,  especially  those  that  are 
so  accurate  and  comprehensive  as  this  one.  The 
book  is  in  every  way  creditable  both  to  the  authors 
and  to  the  publishers.— New  York  Medical  Journal, 
May  21, 1887. 


FARQUHARSON,  ROBERT,  M.  I).,  F.  R.  C.  P.,  LL.  !>., 

Lecturer  on  Materia  Medica  at  St.  Mary's  Hospital  Medical  School,  London. 

A  Guide  to  Therapeutics  and  Materia  Medica.  New  (fourth)  American, 
from  the  fourth  English  edition.  Enlarged  and  adapted  to  the  U.  S.  Pharmacopoeia.  By 
FRANK  WOODBURY,  M.  D.,  Professor  of  Materia  Medica  and  Therapeutics  and  Clinical 
Medicine  in  the  Medico-Chirurgical  College  of  Philadelphia.  In  one  handsome  12mo. 
volume  of  581  pages.  Cloth,  $2.50. 

It  may  correctly  be  regarded  as  the  most  modern 
work  of  its  kind.  It  is  concise,  yet  complete. 
Containing  an  account  of  all  remedies  that  have 
a  place  in  the  British  and  United  States  Pharma- 
copoeias, as  well  as  considering  all  non-official  but 


important  new  drugs,  it  becomes  in  fact  a  miniature 

dispensatory. — Pacific  Medical  Journal,  June,  1889. 

An  especially  attractive  feature  is  an  arrange 

ment  by  which  the  physiological  and  therapeutical 


actions  of  various  remedies  are  shown  in  parallel 
columns.  This  aids  greatly  in  fixing  attention  and 
facilitates  study.  The  American  editor  has  en- 
larged the  work  so  as  to  make  it  include  all  the 
remedies  and  preparations  in  the  U.  S.  Pharma- 
copoeia. The  book  is  a  most  valuable  addition  to 
the  list  of  treatises  on  this  most  important  subject. 
— American  Practitioner  and  News,  Nov.  9th,  1889. 


JSDES,  ROBERT  T.,  M.  !>., 

Jackson  Professor  of  Clinical  Medicine  in  Harvard  University,  Medical  Department. 

A  Text-Book  of  Therapeutics  and  Materia  Medica.    Intended  for  the 
Use  of  Students  and  Practitioners.    Octavo,  544  pages.    Cloth,  $3.50 ;  leather,  $4.50. 


The  present  work  seems  destined  to  take  a  promt 
nent  place  as  a  text-book  on  the  subjects  of  which 
it  treats.  It  possesses  all  the  essentials  which  we 
expect  in  a  book  of  its  kind,  such  as  conciseness, 
clearness,  a  judicious  classification,  and  a  reason- 
able degree  of  dogmatism.  All  the  newest  drugs 
of  promise  are  treated  of.  The  clinical  index  at 
the  end  will  be  found  very  useful.  We  heartily 


commend  the  book  and  congratulate  the  author 
on  having  produced  so  good  a  one.— N.  T.  Medical 
Journal,  Feb.  18, 1888. 

Dr.  Edes'  book  represents  better  than  any  older 
book  the  practical  therapeutics  of  the  present 
day.  The  book  is  a  thoroughly  practical  one.  The 
classification  of  remedies  has  reference  to  their 
therapeutic  action.— Pharmaceutical  Era,  Jan.  1888. 


BRUCE,  J.  MITCHELL,  M.  &.,  F.  R.  C.  P., 

Physician  and  Lecturer  on  Materia  Medica  and  Therapeutics  at  Charing  Cross  Hospital,  London. 

Materia  Medica  and  Therapeutics.  An  Introduction  to  Rational  Treatment. 
Fourth  edition.  12mo.,  591  pages.  Cloth,  $1.50.  See  Students?  Series  of  Manuals,  page  31. 

GRIFFITH,  ROBERT  EGLESFIELV,  M.  p. 

A  Universal  Formulary,  containing  the  Methods  of  Preparing  and  Adminis- 
tering Officinal  and  other  Medicines.  The  whole  adapted  to  Physicians  and  Pharmaceut- 
ists. Third  edition,  thoroughly  revised,  with  numerous  additions,  by  JOHN  M.  MAISCH, 
Phar.D.,  Professor  of  Materia  Medica  and  Botany  in  the  Philadelphia  College  of  Pharmacy. 
In  one  octavo  volume  of  775  pages,  with  38  illustrations  Cloth,  $4.50 ;  leather,  $5.50. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Pathol.,  Histol. 


13 


T.  HENRY,  M.  &., 

Lecturer  on  Pathology  and  Morbid  Anatomy  at  Charing-Cross  Hospital  Medical  School,  London. 

Pathology  and  Morbid  Anatomy.  New  (sixth)  American  from  the  seventh 
revised  English  edition.  Octavo,  539  pp.,  with  167  engravings.  Cloth,  $2.75.  Just  ready. 
The  Pathology  and  Morbid  Anatomy  of  Dr.  translated  into  English,  are  too  abstruse  for  the 
Green  is  too  well  known  by  members  of  the  medi- 
cal profession  to  need  any  commendation.  There 
is  scarcely  an  intelligent  physician  anywhere  who 
has  not  the  work  in  his  library,  for  it  is  almost  an 
essential.  In  fact  it  is  better  adapted  to  the  wants 
of  general  practitioners  than  any  work  of  the  kind 
with  which  we  are  acquainted.  The  works  of 
German  authors  upon  pathology,  which  have  been 


physician.  Dr.  Green's  work  precisely  meets  his 
wishes.  The  cuts  exhibit  the  appearances  of 
pathological  structures  just  as  they  are  seen 
through  the  microscope.  The  fact  that  it  is  so 
generally  employed  as  a  text-book  by  medical  stu- 
dents is  evidence  that  we  have  not  spoken  too 
much  in  its  favor.— Cincinnati  Medical  News,  Oct. 


PAYNE,  JOSEPH  F.,  M.  D.,  F.  It.  C.  P., 

Senior  Assistant  Physician  and  Lecturer  on  Pathological  Anatomy,  St.  Thomas'1  Hospital,  London. 
A  Manual  of  General  Pathology.     Designed  as  an  Introduction  to  the  Prac- 
tice of  Medicine.    Octavo  of  524  pages,  with  152  illus.  and  a  colored  plate.    Cloth,  $3.50. 
Knowing,  as  a  teacher  and  examiner,  the  exact  |  cal  factors  in  those  diseases  now  with  reasonable 


needs  of  medical  students,  the  author  has  in  the 
work  before  us  prepared  for  their  especial  use 
what  we  do  not  hesitate  to  say  is  the  best  introduc- 
tion to  general  pathology  that  we  have  yet  ex- 
amined. A  departure  which  our. author  has 
taken  is  the  greater  attention  paid  to  the  causa- 
tion of  disease,  and  more  especially  to  the  etiologi- 


certainty  ascribed  to  pathogenetic  microbes.  In 
this  department  he  has  been  very  full  and  explicit, 
not  only  in  a  descriptive  manner,  but  in  the  tech- 
nique of  investigation.  The  Appendix,  giving 
methods  of  research,  is  alone  worth  the  price  of  the 
book,  several  times  over,  to  every  student  of 
pathology.— St.  Louis  Med.  and  Surg.  Jour.,  Jan. '89. 


SENN,  NICHOLAS,  M.D.,  Ph.D., 

Professor  of  Principles  of  Surgery  and  Surgical  Pathology  in  Rush  Medical  College,  Chicago. 
Surgical  Bacteriology.    New   (second)   edition.    In  one  handsome  octavo 
about  250  pages,  with  13  plates,  of  which  9  are  colored.     In  press. 


of 


COATS,  JOSEPH,  M.  D.,  F.  F.  P.  S., 

Pathologist  to  the  Glasgow  Western  Infirmary. 

A  Treatise  on  Pathology.    In  one  very  handsome  octavo  volume  of  829  pages, 
with  339  beautiful  illustrations.     Cloth,  $5.50 ;  leather,  $6.50. 


Medical  students  as  well  as  physicians,  who 
desire  a  work  for  study  or  reference,  that  treats 
the  subjects  in  the  various  departments  in  a  very 
thorough  manner,  but  without  prolixity,  will  cer- 
tainly give  this  one  the  preference  to  any  with 
which  we  are  acquainted.  It  sets  forth  the  most 
recent  discoveries,  exhibits,  in  an  interesting 


manner,  the  changes  from  a  normal  condition 
effected  in  structures  by  disease,  and  points  out 
the  characteristics  of  various  morbid  agencies, 
so  that  they  can  be  easily  recognized.  But,  not 
limited  to  morbid  anatomy,  it  explains  fully  how 
the  functions  of  organs  are  disturbed  by  abnormal 
conditions.— Cincinnati  Medical  News,  Oct.  1883. 


GIBBES,  HENEAGE,  M.  !>., 

Professor  of  Pathology  in  the  University  of  Michigan,  Medical  Department. 

Practical  Pathology.    In  one  very  handsome  octavo  volume  of  about  400  pages, 
with  about  75  illustrations.    In  press. 


WOODHEAD,  G.  SIMS,  M.  &.,  F.  U.  C.  P.,  E.9 

Demonstrator  of  Pathology  in  the  University  of  Edinburgh. 

Practical  Pathology.    A  Manual  for  Students  and  Practitioners.    In  one  beau- 
tiful octavo  volume  of  497  pages,  with  136  exquisitely  colored  illustrations.     Cloth,  $6.00. 

SCHAFEB,  EDWARD  A.,  F.  R.  S., 

Jodrell  Professor  of  Physiology  in  University  College,  London. 

The  Essentials  of  Histology.     In  one  octavo  volume  of  246  pages,  with 
281  illustrations.    Cloth,  $2.25. 

cially  adapted  for  laboratory  work,  at  the  same 

has  been  written  with  the   object  "of  supplying    time   it  is  intended  to  serve  as  an  elementary 
the  student  with  directions  for  the  microscopical 
examination  of  the  tissues,  which  are  given  in  a 
clear  and  understandable  way.     Although  espe- 


text-book  of  histology,  comprising  all  the  essen- 
tial facts  of  the  science.— The  Physician  and  Sur- 


geon, July,  1887. 


KLEIN,  E.,  M.  D.,  F.  R.  S., 

Joint  Lecturer  on  General  Anat.  and  Phys.  in  the  Med.  School  of  St.  Bartholomew's  Hosp.,  London. 
Elements  of  Histology.     Fourth  edition.    In  one  12mo.  volume  of  376  pages, 
with  194  illus.    Limp  cloth,  $1.75.      See  Students?  Series  of  Manuals,  page  31. 

Considered  with  regard  to  its  contents,  it  can  '  index  affords  a  ready  reference  to  the  histology  of 
only  be  looked  on  as  a  large  and  comprehensive 
volume.   New  and  original  illustrations  have  been 
added,  with  the  help  of  which  the  structure  of  each 
tissue  becomes  clear  to  the  reader.    A  copious 


every  tissue  and  organ,  and  presents,  at  the  same 
time,  a  complete  glossary  of  the  scientific  terms.— 
Provincial  Medical  Journal,  May  1, 1889. 


PEPPER,  A.  J.,  M.  B.,  M.  S.,  F.  R.  C.  S., 

Surgeon  and  Lecturer  at  St.  Mary's  Hospital,  London. 

Surgical  Pathology.     In  one  pocket-size  12mo.  volume  of  511  pages,  with  81 
illustrations.  Limp  cloth,  red  edges,  $2.00.    See  Students'  Series  of  Manuals,  page  31. 


14 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Practice  of  Med. 


FLINT,  AUSTIN,  M.  D.,  LL.  D., 

Prof,  of  the  Principles  and  Practice  of  Med.  and  of  din.  Med.  in  Bellevue  Hospital  Medical  College,  N.  Y. 

A  Treatise  on  the  Principles  and  Practice  of  Medicine.  Designed  for 
the  use  of  Students  and  Practitioners  of  Medicine.  New  (sixth)  edition,  thoroughly  re- 
vised and  rewritten  by  the  Author,  assisted  by  WILLIAM  H.  WELCH,  M.  D.,  Professor  of 
Pathology,  Johns  Hopkins  University,  Baltimore,  and  AUSTIN  FLINT,  JR.,  M.  D.,  LL.  D., 
Professor  of  Physiology,  Bellevue  Hospital  Medical  College,  N.  Y.  In  one  very  handsome 
octavo  volume  of  1160  pages,  with  illustrations.  Cloth,  $5.50;  leather,  $6.50. 

No  text-book  on  the  principles  and  practice  of  I 
medicine  has  ever  met  in  this  country  with  such  ' 
general  approval  by  medical  students  and  practi- 
tioners as  the  work  of  Professor  Flint.  In  all  the 
medical  colleges  of  the  United  States  it  is  the  fa- 
vorite work  upon  Practice;  and,  as  we  have  stated 
before  in  alluding  to  it,  there  is  no  other  medical 
work  that  can  be  so  generally  found  in  the  libra- 
ries of  physicians,  in  every  state  and  territory 
of  this  vast  country  the  book  that  will  be  most  likely 
to  be  found  in  the  office  of  a  medical  man,  whether 


in  city,  town,  village,  or  at  some  cross-roads,  is 
Flint's  Practice.  We  make  this  statement  to  a 
considerable  extent  from  personal  observation,  and 
it  is  the  testimony  also  of  others.  An  examina- 
tion shows  that  very  considerable  changes  have 
been  made  in  the  sixth  edition.  The  work  may  un- 
doubtedly be  regarded  as  fairly  representing  the 
present  state  of  the  science  of  medicine,  and  as 
reflecting  the  views  of  those  who  exemplify  in 
their  practice  the  present  stage  of  progress  of  med- 
ical art.— Cincinnati  Medical  Newt,  Oct.  1886. 


BRISTOWE,  JOHN  SYER,  M.  D.,  LL.  D.,  F.  R.  S., 

Senior  Physician  to  and  Lecturer  on  Medicine  at  St.  Thomas1  Hospital,  London. 

A  Treatise  on  the  Science  and  Practice  of  Medicine.     Seventh  edi- 
tion.    In  one  large  octavo  volume  of  1325  pages.     Cloth,  $6.50 ;  leather,  $7.50.    Just  ready. 


The  remarkable  regularity  with  which  new  edi- 
tions of  this  text-book  make  their  appearance  is 
striking  testimony  to  its  excellence  and  value. 
This,  too,  in  spite  of  the  numerous  rivals  for  the 
favor  of  the  student  which  have  been  put  forth 
within  the  sixteen  years  since  Bristowe's"  Medi- 
cine "  first  appeared.  Nor  can  it  be  said  that  the 
author  himself  has  failed  to  keep  his  manual 
abreast  of  advancing  knowledge,  arduous  as  that 
task  must  prove.  So  long  as  there  is  shown  such 
care  and  circumspection  in  the  inclusion  of  all 
new  matter  that  has  stood  the  test  of  criticism,  so 
long  will  this  work  retain  the  favor  which  it  has 
always  met.  For  it  is  a  work  that  is  built  on  a 
stable  foundation,  systematic,  scientific  and  prac- 
tical, containing  the  matured  experience  of  a 


physician  who  has  every  claim  to  be  considered 
an  authority,  and  composed  in  a  style  which  at- 
tracts the  practitioner  as  much  as  the  student.  No 
one  can  say  that  this  book  has  obtained  a  success 
which  was  undeserved,  and  we  trust  that  its  author 
will  long  continue  to  supervise  the  production  of 
fresh  editions  for  the  advantage  of  the  coming 
generation  of  medical  students. — The  Lancet,  July 
12,  1890. 

Dr.  Bristowe's  now  famous  treatise  appears  in 
its  seventh  edition.  It  has  long  passed  the  stage 
in  which  it  requires  critical  examination  or  com- 
mendation, and  has  thoroughly  established  itself 
as  among  the  most  complete  and  useful  of  text- 
books.— British  Medical  Journal,  September  27, 1890. 


HARTSHORNE,  HENRY,  M.  D.,  LL.  D., 

Lately  Professor  of  Hygiene  in  the  University  of  Pennsylvania. 

Essentials  of  the  Principles  and  Practice  of  Medicine.  A  Handbook 
for  Students  and  Practitioners.  Fifth  edition,  thoroughly  revised  and  rewritten.  In  one 
royal  12mo.  volume  of  669  pages,  with  144  illustrations.  Cloth,  $2,75 ;  half  bound,  $3.00. 

Within  the  compass  of  600  pages  it  treats  of  the 
history  of  medicine,  general  pathology,  general 
symptomatology,  and  physical  diagnosis  (including 
laryngoscope,  ophthalmoscope,  etc.),  general  ther- 
apeutics, nosology,  and  special  pathology  and  prac- 
tice. There  is  a  wonderful  amount  of  information 
contained  in  this  work,  and  it  is  one  of  the  best 
of  its  kind  that  we  have  seen.— Glasgow  Medical 
Journal,  Nov.  1882. 

An  indispensable  book.  No  work  ever  exhibited 
a  better  average  of  actual  practical  treatment  than 


this  one;  and  probably  not  one  writer  in  our  day 
had  a  better  opportunity  than  Dr.  Hartshorne  for 
condensing  all  the  views  of  eminent  practitioners 
into  a  12mo.  The  numerous  illustrations  will  be 
very  useful  to  students  especially.  These  essen- 
tials, as  the  name  suggests,  are  not  intended  to 
supersede  the  text-books  of  Flint  and  Bartholow, 
but  they  are  the  most  valuable  in  affording  the 
means  to  see  at  a  glance  the  whole  literature  of  any 
disease,  and  the  most  valuable  treatment.— Chicago 
Medical  Journal  and  Examiner,  April,  1882. 


REYNOLDS,  J.  RUSSELL,  M.  D., 

Professor  of  the  Principles  and  Practice  of  Medicine  in  University  College,  London. 

A  System  of  Medicine.  With  notes  and  additions  by  HENRY  HARTSHORNE, 
A.  M.,  M.  D.,  late  Professor  of  Hygiene  in  the  University  of  Pennsylvania.  ^  In  three  large 
and  handsome  octavo  volumes,  containing  3056  double-columned  pages,  with  317  illustra- 
tions. Price  per  volume,  cloth,  $5.00 ;  sheep,  $6.00 ;  very  handsome  half  Kussia,  raised  bands, 
$6.50.  Per  set,  cloth,  $15;  leather,  $18.  Sold  only  by  subscription. 


STILLE,  ALFRED,  M.  JO.,  LL.  D., 

Professor  Emeritus  of  the  Theory  and  Practice  of  Med.  and  of  Clinical  Med.  in  the  Univ.  of  Penna. 
Cholera :   Its  Origin,  History,  Causation,  Symptoms,  Lesions,  Prevention  and  Treat- 
ment. In  one  handsome  12mo.  volume  of  163  pages,  with  a  chart.  Cloth,  $1.25. 

WATSON,  SIR  THOMAS,  M.  D., 

Late  Physician  in  Ordinary  to  the  Queen. 

Lectures  on  the  Principles  and  Pra9tice  of  Physic.  A  new  American 
from  the  fifth  English  edition.  Edited,  with  additions,  and  190  illustrations,  by  HENRY 
HARTSHORNE,  A.  M.,  M.  D.,  late  Professor  of  Hygiene  in  the  University  of  Pennsylvania. 
In  two  large  octavo  volumes  of  1840  pages.  Cloth,  $9.00  ;  leather,  $11.00. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — System  of  Med. 


15 


For  Sale  by  Subscription  Only. 


A  System  of  Practical  Medicine. 

BY  AMERICAN  AUTHORS. 

EDITED  BY  WILLIAM  PEPPER,  M.  D.,  LL.  D., 

PROVOST  AND  PROFESSOR  OP  THE  THEORY  AND  PRACTICE  OF  MEDICINE  AND  OF 
CLINICAL  MEDICINE  IN  THE  UNIVERSITY  OF  PENNSYLVANIA, 

Assisted  by  Louis  STARR,  M.  D.,  Clinical  Professor  of  the  Diseases  of  Children  in  the 
Hospital  of  the  University  of  Pennsylvania. 

The  complete  work,  in  five  volumes,  containing  5573  pages,  with  198  illustrations,  is  now  ready. 
Price  per  volume,  cloth,  $5;  leather,  $6 ;  half  Russia,  raised  bands  and  open  back,  $7. 

In  this  great  work  American  medicine  is  for  the  first  time  reflected  by  its  worthiest 
teachers,  and  presented  in  the  full  development  of  the  practical  utility  which  is  its  pre- 
eminent characteristic.  The  most  able  men — from  the  East  and  the  West,  from  the 
North  and  the  South,  from  all  the  prominent  centres  of  education,  and  from  all  the 
hospitals  which  afford  special  opportunities  for  study  and  practice — have  united  in 
generous  rivalry  to  bring  together  this  vast  aggregate  of  specialized  experience. 

The  distinguished  editor  has  so  apportioned  the  work  that  to  each  author  has  been 
assigned  the  subject  which  he  is  peculiarly  fitted  to  discuss,  and  in  which  his  views 
will  be  accepted  as  the  latest  expression  of  scientific  and  practical  knowledge.  The 
practitioner  will  therefore  find  these  volumes  a  complete,  authoritative  and  unfailing  work 
of  reference,  to  which  he  may  at  all  times  turn  with  full  certainty  of  finding  what  he  needs 
in  its  most  recent  aspect,  whether  he  seeks  information  on  the  general  principles  of  medi- 
cine, or  minute  guidance  in  the  treatment  of  special  disease.  So  wide  is  the  scope  of  the 
work  that,  with  the  exception  of  midwifery  and  matters  strictly  surgical,  it  embraces  the 
whole  domain  of  medicine,  including  the  departments  for  which  the  physician  is  accustomed 
to  rely  on  special  treatises,  such  as  diseases  of  women  and  children,  of  the  genito-urinary 
organs,  of  the  skin,  of  the  nerves,  hygiene  and  sanitary  science,  and  medical  ophthalmology 
and  otology.  Moreover,  authors  have  inserted  the  formulas  which  they  have  found  most 
efficient  in  the  treatment  of  the  various  affections.  It  may  thus  be  truly  regarded  as  a 
COMPLETE  LIBRARY  OF  PRACTICAL  MEDICINE,  and  the  general  practitioner  possessing  it 
may  feel  secure  that  he  will  require  little  else  in  the  daily  round  of  professional  duties. 

In  spite  of  every  effort  to  condense  the  vast  amount  of  practical  information  fur- 
nished, it  has  been  impossible  to  present  it  in  less  than  5  large  octavo  volumes,  containing 
about  5600  beautifully  printed  pages,  and  embodying  the  matter  of  about  15  ordinary 
octavos.  Illustrations  are  introduced  wherever  requisite  to  elucidate  the  text. 

,  A  detailed  prospectus  will  be  sent  to  any  address  on  application  to  the  publishers. 


These  two  volumes  bring  this  admirable  work 
to  a  close,  and  fully  sustain  the  high  standard 
reached  by  the  earlier  volumes;  we  have  only 
therefore  to  echo  the  eulogium  pronounceu  upon 
them.  We  would  warmly  congratulate  the  editor 
and  his  collaborators  at  the  conclusion  of  their 
laborious  task  on  the  admirable  manner  in  which, 
from  first  to  last,  they  have  performed  their  several 
duties.  They  have  succeeded  in  producing  a 
work  which  will  long  remain  a  standard  work  of 
reference,  to  which  practitioners  will  look  for 
guidance,  and  authors  will  resort  for  facts. 
From  a  literary  point  of  view,  the  work  is  without 
any  serious  blemish,  and  in  respect  of  production, 
it  has  the  beautiful  finish  that  Americans  always 
give  their  works. — Edinburgh  Medical  Journal.  Jan. 
1887. 

*  *  The  greatest  distinctively  American  work  on 
the  practice  of  medicine,  and,  indeed,  the  super- 
lative adjective  would  not  be  inappropriate  were 
even  all  other  productions  placed  in  comparison. 
An  examination  of  the  five  volumes  is  sufficient 
to  convince  one  of  the  magnitude  of  the  enter- 
prise, and  of  the  success  which  has  attended  its 
fulfilment.—  The  Medical  Age,  July  26, 1886. 

This  huge  volume  forms  a  fitting  close  to  the 

treat  system  of  medicine  which  in  so  short  a  time 
as  won  so  high  a  place  in  medical  literature,  and 
has  done  such  credit  to  the  profession  in  this 
country.  Among  the  twenty-tnree  contributors 
are  the  names  of  the  leading  neurologists  in 
America,  and  most  of  the  work  in  the  volume  is  of 
the  highest  order. — Boston  Medical  and  Surgical 
Journal,  July  21, 1887. 

We  consider  it  one  of  the  grandest  works  on 
Practical  Medicine  in  the  English  language.  It  is 
a  work  of  which  the  profession  of  this  country  can 
feel  proud.  Written  exclusively  by  American 


physicians  who  are  acquainted  with  all  the  varie 
ties  of  climate  in  the  United  States,  the  character 
of  the  soil,  the  manners  and  customs  of  the  peo- 
ple, etc.,  it  is  peculiarly  adapted  to  the  wants 
of  American  practitioners  of  medicine,  and  it 
seems  to  us  that  every  one  of  them  would  desire 
to  have  it.  It  has  been  truly  called  a  "  Complete 
Library  of  Practical  Medicine,"  and  the  general 
practitioner  will  require  little  else  in  his  round 
of  professional  duties. — Cincinnati  Medical  News, 
March,  1886. 

Each  of  the  volumes  is  provided  with  a  most 
copious  index,  and  the  work  altogether  promises 
to  be  one  which  will  add  much  to  the  medical 
literature  of  the  present  century,  and  reflect  great 
credit  upon  the  scholarship  and  practical  acumen 
of  its  authors.—  The  London  Lancet,  Oct.  3, 1885. 

The  feeling  of  proud  satisfaction  with  which  the 
American  profession  sees  this,  its  representative 
system  of  practical  medicine  issued  to  the  medi- 
cal world,  is  fully  justified  by  the  character  of  the 
work.  The  entire  caste  of  the  system  is  in  keep- 
ing with  the  best  thoughts  of  the  leaders  and  fol- 
lowers of  our  home  school  of  medicine,  and  the 
combination  of  the  scientific  study  of  disease  and 
the  practical  application  of  exact  and  experimen- 
tal knowledge  to  the  treatment  of 'human  mal- 
adies, makes  every  one  of  us  share  in  the  pride 
that  has  welcomed  Dr.  Pepper's  labors.  Sheared 
of  the  prolixity  that  wearies  the  readers  of  the 
German  school,  the  articles  glean  these  same 
fields  for  all  that  is  valuable.  It  is  the  outcome 
of  American  brains,  and  is  marked  throughout 
by  much  of  the  sturdy  independence  of  thought 
and  originality  that  is  a  national  characteristic. 
Yet  nowhere  is  there  lack  of  study  of  the  most 
advanced  views  of  the  day. — North  Carolina  Medi- 
cal Journal,  Sept.  1886. 


16 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Clinical  Mecl.,  etc. 


FOTHERGILL,  J.  M.,  M.  D.,  Edin.,  M.  R.  C.  P.,  Land.. 

Physician  to  the  City  of  London  Hospital  fa*  Diseases  of  the  Chest. 

The  Practitioner's  Handbook  of  Treatment  ;  Or,  The  Principles  of  Thera- 
peutics.  New  (third)  edition.    In  one  8vo.  vol.  of  661  pages.    Cloth,  $3.75  ;  leather,  $4.75. 

This  is  a  wonderful  book.    If  there  be  such  & 
thing  as  "medicine  made  easy,"  this  is  the  work  to 
accomplish  this  result.—  Fa.  Med.  Month.,  June,'87. 
It  is  an  excellent,  practical  work  on  therapeutics, 
well  arranged  and  clearly  expressed,  useful  to  the 


To  have  a  description  of  the  normal  physiologi- 
cal processes  of  an  organ  and  of  the  methods  of 
treatment  of  its  morbid  conditions  brought 
together  in  a  single  chapter,  and  the  relations 
between  the  two  clearly  stated,  cannot  fail  to  prove 
a  great  convenience  to  many  thoughtful  but  busy 
physicians.  The  practical  value  of  the  volume  is 
greatly  increased  by  the  introduction  of  many 
prescriptions.  That  the  profession  appreciates 
that  the  author  has  undertaken  an  important  work 
and  has  accomplished  it  is  shown  by  the  demand 
for  this  third  edition.—^.  Y.  Med.  Jour.,  June  11,'87. 


to  the 

student  and  young  practitioner,  perhaps  even  to 
the  old.  —  Dublin  Journal  of  Medical  Science,  March, 
1888. 

We  do  not  kn«w  a  more  readable,  practical  and 
useful  work  on  the  treatment  of  disease  than  the 
one  we  have  now  before  us.—  Pacific  Medical  and 
Surgical  Journal,  October,  1887. 


VATIGHAN,  VICTOR  C.,  Ph.  D.,  M.  D., 

Prof.  ofPhys.  and  Path.  Chem.  and  Assoc.  Prof,  of  Therap.  and  Mat.  Med.  in  the  Univ.  of  Mich. 

and  NOVY,  FREDERICK  G.,  M.  D. 

Instructor  in  Hygiene  and  Phys.  Chem.  in  the  Univ.  of  Mich. 

Ptomaines  and  Leucomaines,  or  Putrefactive  and  Physiological 
Alkaloids.  New  Edition.  In  one  handsome  12mo.  vol.  of  about  300  pages.  Preparing. 

FINLAYSON,  JAMES,  M.  D.,  Editor, 

Physician  and  Lecturer  on  Clinical  Medicine  in  the  Glasgow  Western  Infirmary,  etc. 

Clinical  Manual  for  the  Study  of  Medical  Cases.  With  Chapters 
by  Prof.  Gairdner  on  the  Physiognomy  of  Disease;  Prof.  Stephenson  on  Diseases  of 
the  Female  Organs ;  Dr.  Robertson  on  Insanity ;  Dr.  Gemmell  on  Physical  Diagnosis ; 
Dr.  Coats  on  Laryngoscopy  and  Post-Mortem  Examinations,  and  by  the  Editor  on  Case- 
taking,  Family  History  and  Symptoms  of  Disorder  in  the  Various  Systems.  New  edition. 
In  one  12mo.  volume  of  682  pages,  with  158  illustrations.  Cloth,  $2.50. 

treatise  on  medical  diagnosis,  in  which  every  sign 
and  symptom  of  disease  is  carefully  analyzed,  and 
their  relative  significance  in  the  different  affec- 
tions in  which  they  occur  pointed  out.  From  their 
synthesis  the  student  can  accurately  determine 
the  disease  with  which  he  has  to  deal.  The  book 
has  no  competitor,  nor  is  it  likely  to  have  as  long 
as  future  editions  maintain  its  present  standard  of 


The  profession  cannot  but  welcome  the  second 
edition  of  this  very  valuable  work  of  Finlayson 
and  his  collaborators.  The  size  of  the  book  has 
been  increased  and  the  number  of  illustrations 
nearly  doubled.  The  manner  in  which  the  subject 
is  treated  is  a  most  practical  one.  Symptoms 
alone  and  their  diagnostic  indications  form  the 
basis  of  discussion.  The  text  explains  clearly  and 
fully  the  methods  of  examinations  and  the  con- 
clusions to  be  drawn  from  the  physical  signs.— 
The  Medical  News,  April  23, 1887. 

We  are  pleased  to  see  a  second  edition  of  this 
admirable  book.  It  is  essentially  a  practical 


excellence.  The  general  practitioner  will  find 
many  practical  hints  in  its  pages,  while  a  careful 
study  of  the  work  will  save  him  from  many  pitfalls 
in  diagnosis.— Liverpool  Medico- Chirurgical  Jour- 
nal, January,  1887. 


BROADBENT,  W.  H.,  M.  D.,  F.  R.  C.  P., 

Physician  to  and  Lecturer  on  Medicine  at  St.  Mary's  Hospital,  London. 

The  Pulse.     In  one  12mo.  volume  of  312  pages.    Cloth,  $1.75.    See  Series  of  Clin- 
ical Manuals,  page  31 

This  little  book  probably  represents  the  best 
practical  thought  on  this  subject  in  the  English 
language.  A  correct  interpretation  of  the  pulse, 
with  its  almost  infinite  modifications,  brought 
about  by  almost  unlimited  bodily  variations,  can 


only  be  achieved  by  experience,  and,  as  an  aid 
toward  attaining  this  goal,  nothing  will  be  of  more 
service  than  this  brochure  on  the  study  of  the 
pulse. — The  American  Journal  of  Medical  Sciences, 
Set  '  -  — 


jptember,  1890. 

HABERSHON,  S.  O.,  M.  D., 

Senior  Physician  to  and  late  Lect.  on  Principles  and  Practice  of  Med.  at  Quy's  Hospital,  London. 

On  the  Diseases  of  the  Abdomen ;  Comprising  those  of  the  Stomach,  and 
other  parts  of  the  Alimentary  Canal,  (Esophagus,  Caecum,  Intestines  and  Peritoneum.  Second 
American  from  third  enlarged  and  revised  English  edition.  In  one  handsome  octavo 
volume  of  554  pages,  with  illustrations. .  Cloth,  $3.50. 

to  the  times,  and  making  it  a  volume  of  interest  to 


This  valuable  treatise  on  diseases  of  the  stomach 
and  abdomen  will  be  found  a  cyclopaedia  of  infor- 
mation, systematically  arranged,  on  all  diseases  of 
the  alimentary  tract,  from  the  mouth  to  the 
rectum.  A  fair  proportion  of  each  chapter  is 


The  present  edition  is  fuller  than  former  ones  in 


the  practitioner  in  every  field  of  medicine  and 
surgery.  Perverted  nutrition  is  in  some  form 
associated  with  all  diseases  we  have  to  combat, 
and  we  need  all  the  light  that  can  be  obtained  on 
a  subject  so  broad  and  general.  Dr.  Habershon's 
work  is  one  that  every  practitioner  should  read 
"  study  for  himself.— N.  Y.  Medical  Journal, 


many  particulars,  and  has  been  thoroughly  revised  and  study 
and  amended  by  the  author.  Several  new  chap-  j  April,  1879. 
ters  have  been  added,  bringing  the  work  fully  up  I  

TANNER,  THOMAS  HAWKES,  M.  J). 

A  Manual  of  Clinical  Medicine  and  Physical  Diagnosis.  Third  American 
from  the  second  London  edition.  Kevised  and  enlarged  by  TILBURY  Fox,  M.  D. 
In  one  small  12mo.  volume  of  362  pages,  with  illustrations.  Cloth,  $1.50. 


LECTURES  ON  THE  STUDY  OF  FEVER.  By 
A.  HUDSON,  M.  D.,  M.  R.  I.  A.  In  one  octavo 
volume  of  308  pages.  Cloth,  $2.50. 

A  TREATISE  ON  FEVER.  By  ROBERT  D.  LYONS, 
K.  C.  C.  In  one  8vo.  vol.  of  354  pp.  Cloth,  $2.25. 


LA  ROCHE  ON  YELLOW  FEVER,  considered  in 
its  Historical,  Pathological,  Etiological  and 
Therapeutical  Relations.  In  two  large  and  hand- 
some octavo  volumes  of  1468  pp.  Cloth,  $7.00. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Hygiene,  Electr.,  Pract.        17 


BARTHOLOW,  ROBERTS,  A.  M.,  M.  D.,  LL.  D., 

Prof,  of  Materia  Medico,  and  General  Therapeutics  in  the  Jefferson  Med.  Coll.  of  Phila.,  etc. 
Medical  Electricity.     A  Practical  Treatise  on  the  Applications  of  Electricity 
to  Medicine  and  Surgery.    New  (third)  edition.    In  one  very  handsome  octavo  volume  of 
308  pages,  with  110  illustrations.    Cloth,  $2.50. 

The  fact  that  this  work  has  reached  its  third  edi- 
tion in  six  years,  and  that  it  has  been  kept  fully 
abreast  with  the  increasing  use  and  knowledge  of 
electricity,demonstrates  its  claim  to  be  considered 
a  practical  treatise  of  tried  value  to  the  profession. 
The  matter  added  to  the  present  edition  embraces 


the  most  recent  advances  in  electrical  treatment. 
The  illustrations  are  abundant  and  clear,  and  the 
work  constitutes  a  full,  clear  and  concise  manual 
well  adapted  to  the  needs  of  both  student  and 
practitioner.—  The  Medical  News,  May  14, 1887. 


YEO,  I.  BTJRNEY,  M.  D.,  F.  M.  C.  P., 

Professor  of  Clinical  Therapeutics  in  King's   College,  London,  and  Physician  to  King's  College 
Hospital. 


Food  in  Health  and  Disease. 

See  Series  of  Clinical  Manuals,  page  31. 


Dr.  Yeo  supplies  in  a  compact  form  nearly  all  that 
the  practitioner  requires  to  know  on  the  subject  of 
diet.  The  work  is  divided  into  two  parts— food  in 
health  and  food  in  disease.  Dr.  Yeo  has  gathered 
together  from  all  quarters  an  immense  amount  of 
useful  information  within  a  comparatively  small 


In  one  12mo.  volume  of  590  pages.    Cloth,  $2. 


compass,  and  he  has  arranged  and  digested  his 


materials  with  skill  for  the  use  of  the  practitioner. 
We  have  seldom  seen  a  book  which  more  thor- 
oughly realizes  the  object  for  which  it  was  written 
than  this  little  work  of  Dr.  Yeo.— British  Medical 
Journal,  Feb.  8, 1890. 

^RICHARDSON,  B.  W.,  M.D.,  LL.  D.,  F.R.S., 

Fellow  of  the  Royal  College  of  Physicians,  London. 
Preventive  Medicine.   In  one  octavo  volume  of  729  pages.   Cloth,  $4;  leather.  $5. 


Dr.  Richardson  has  succeeded  in  producing 
work  which  is  elevated  in  conception,  comprehen- 
sive in  scope,  scientific  in  character,  systematic  in 
arrangement,  and  which  is  written  in  a  clear,  con- 
•cise  and  pleasant  manner.  He  evinces  the  happy 
faculty  oi  extracting  the  pith  of  what  is  known  on 
the  subject,  and  of  presenting  it  in  a  most  simple, 
intelligent  and  practical  form.  There  is  perhaps 
no  similar  work  written  for  the  general  public 
that  contains  such  a  complete,  reliable  and  instruc- 


tive collection  of  data  upon  the  diseases  common 
to  the  race,  their  origins,  causes,  and  the  measures 
for  their  prevention.  The  descriptions  of  diseases 
are  clear,  chaste  and  scholarly ;  the  discussion  of 
the  question  of  disease  is  comprehensive,  masterly 
and  fully  abreast  with  the  latest  and  best  knowl- 
edge on  the  subject,  and  the  preventive  measures 
advised  are  accurate,  explicit  and  reliable.— The 
American  Journal  of  the  Medical  Sciences,  April,  1884. 


THE  YEAR-BOOK  OF  TREATMENT  FOR  1891. 

A  Comprehensive  and  Critical  Review  for  Practitioners  of  Medi- 
cine.    In  one  12mo.  volume  of  484  pages.    Cloth,  $1.50.    Just  ready. 
*\  For  special  commutations  with  periodicals  see  pages  1  and  2. 

Heart  and  Circulation.    By  J.  MITCHELL  BRUCE,  M.  D.,  F.  R.  C.  P. Lungs  and  Organs  of  Respira- 
tion,    by  E.  MABKHAM  SKERRITT,  M.  D.,  F.  R.  C.  P. Nervous  System.    By  JAMES  Ross,  M.  D.,  LL.  D., 

F.  R.  C.  P.,  and  ERNEST  SEPTIMUS  REYNOLDS.  M.  D.,  M.  R.  C.  P. Stomach,  Intestines,  Liver,  etc.    By 

ROBERT  MAGUIRE,  M,  D.,  F.  R.  C.  P. Kidney,  Diabetes,  etc.     By  CHARLES  H.  RALFE,  M.  A.,  M.  D., 

Cantab.,  F.  R.  C.  P. Gout,  Rheumatism,  and  Rheumatoid  Arthritis.    By  ARCHIBALD  E.  GARROD,  M.  A., 

M.  D.,  Oxon.,  M.  R.  C.  P. Infectious  Fevers.      By  SIDNEY  PHILLIPS,  M.  D.,  M.  R.  C.P. General 

Surgery.  By  STANLEY  BOYD,  B.  S  ,  Lond.,  F.  R.  C.  S. Orthopaedic  Surgery.  By  W.  J.  WALSHAM,  F.R.C.S. 

-Surgical  Diseases  of  Children.     By  EDMUND  OWEN,  M.  B.,  F.  R.  C.  S. Diseases  of  the  Genito- 

Urinary  System.    By  REGINALD  HARRISON,  F.R  C.S. Venereal  Diseases.    By  ALFRED  COOPER,  F.R.C.S. 

Diseases  of  Women.    By  D.  BERRY  HART,  M.  D.,  F.  R.  C.  P.  Ed. — ^-Midwifery.    By  GEORGE  ERNEST 

HERMAN,  M.  B  ,  F.  R.  C.  P. Skin.     By  MALCOLM  MORRIS,  F.  R.  C.  S.  Ed. Eye.     By  HENRY  POWER, 

M.  B.,  F.R.C.S. Ear.    By  GEORGE  P.  FIELD,  M.R.  C.S. Throat  and  Nose.    By  BARCLAY  J.  BARON, 

M.  B.,  C.  M.  Edin. Summary  of  the  Therapeutics  of  the  Year  1889-90.    By  WALTER  G.  SMITH,  M.  D. 


THE  YEAR-  BOOKS  of  TREATMENT  for  >86, 

Similar  to  above.     12mo.,  320-341  pages.    Limp  cloth,  $1.25  each. 

SCHREIBER,  JOSEPH,  M.  D. 

A  Manual  of  Treatment  by  Massage  and  Methodical  Muscle  Ex- 
ercise. Translated  by  WALTER  MENDELSON,  M.  D.,  of  New  York.  In  one  handsome 
octavo  volume  of  274  pages,  with  117  fine  engravings.  Cloth,  $2.75. 


STURGES'  INTRODUCTION  TO  THE  STUDY 
OF  CLINICAL  MEDICINE.  Being  a  Guide  to 
the  Investigation  of  Disease.  In  one  handsome 
12mo.  volume  of  127  pages.  Cloth,  $1.25. 

DAVIS'  CLINICAL  LECTURES  ON  VARIOUS 
IMPORTANT  DISEASES.  By  N.  S.  DAVIS, 
M.  D.  Edited  by  FRANK  H.  DAVIS,  M.  D.  Second 
edition.  12mo.  287  pages.  Cloth,  $1.75. 

TODD'S  CLINICAL  LECTURES  ON  CERTAIN 
ACUTE  DISEASES.  In  one  octavo  volume  of 
820  pages.  Cloth.  $2.50. 

PAVY'S  TREATISE  ON  THE  FUNCTION  OF  DI 
GESTION;  its  Disorders  and  their  Treatment. 
From  the  second  London  edition.  In  one  octavo 
volume  of  238  pages.  Cloth,  $2.00. 

BARLOW'S  MANUAL  OF  THE  PRACTICE  OF 
MEDICINE.  With  additions  by  D.  F.  CONDI  E, 
M.  D.  1  vol.  8vo.,  pp.  603.  Cloth,  $2.50. 

CHAMBERS' MANUAL  OF  DIET  AND  REGIMEN 
IN  HEALTH  AND  SICKNESS.  In  one  hand 
some  octavo  volume  of  302  pp.  Cloth,  $2.75. 


HOLLAND'S  MEDICAL  NOTES  AND  REFLEC- 
TIONS. 1  vol.  8vo.,  pp.  493.  Cloth,  $3.50. 

FULLER  ON  DISEASES  OF  THE  LUNGS  AND 
AIR-PASSAGES.  Their  Pathology,  Physical  Di- 
agnosis, Symptoms  and  Treatment.  From  the 
second  and  revised  English  edition.  In  one 
octavo  volume  of  475  pages.  Cloth,  $3.50. 

WALSHE  ON  THE  DISEASES  OF  THE  HEART 
AND  GREAT  VESSELS.  Third  American  edi- 
tion. In  1  vol.  8vo.,  416  pp.  Cloth,  $3.00. 

SLADE  ON  DIPHTHERIA;  its  Nature  and  Treat- 
ment, with  an  account  of  the  History  of  its  Pre- 
valence in  various  Countries.  Second  and  revised 
edition.  In  one  12mo.  vol.,  158  pp.  Cloth,  $1.25. 

SMITH  ON  CONSUMPTION ;  its  Early  and  Reme- 
diable Stages.  1  vol.  8vo.,  253  pp.  Cloth,  $2.25. 

LA  ROCHE  ON  PNEUMONIA.  1  vol.  8vo.  of  490 
pages.  Cloth,  $3.00. 

WILLIAMS  ON  PULMONARY  CONSUMPTION; 
its  Nature,  Varieties  and  Treatment.  With  an 
analysis  of  one  thousand  cases  to  exemplify  its 
duration.  In  one  8vo.  vol.  of  303  pp.  Cloth,  $2.50. 


18  LEA  BROTHERS  &  Co.'s  PUBLICATIONS— Throat,  Lungs,  Heart,  Nerves. 
FLINT,  AUSTIN,  M.  &.,  LL.  &., 

Professor  of  the  Principles  and  Practice  of  Medicine  in  Bellevue  Hospital  Medical  College,  N.  7. 

A  Manual  of  Auscultation  and  Percussion ;  Of  the  Physical  Diagnosis  of 
Diseases  of  the  Lungs  and  Heart,  and  of  Thoracic  Aneurism.  New  (fifth)  edition. 
Edited  by  James  C.  Wilson,  M.  D.,  Jefferson  Medical  College,  Philadelphia.  In  one 
handsome  royal  12mo.  volume  of  274  pages,  with  12  illustrations.  Cloth,  $1.75.  Just  ready. 

This  little  book  through  its  various  editions  has  j  oughness  of  Prof.  Flint's  investigations.  For  stu- 
probably  done  more  to  advance  the  science  of  dents  it  is  excellent.  Its  value  is  shown  both  in 
physical  exploration  of  the  chest  than  any  other  j  the  arrangement  of  the  material  and  in  the  clear, 
dissertation  upon  the  subject,  and  now  in  its  fifth  concise  style  of  expression.  For  the  practitioner 
edition  it  is  as  near  perfect  as  it  can  be.  The  It  is  a  ready  manual  for  reference.— North  Ameri- 
rapidity  with  which  previous  editions  were  sold  can  Practitioner,  January,  1891. 
shows  how  the  profession  appreciated  the  thor- 


£Y  THE  SAME  A  UTHOR. 

A  Practical  Treatise  on  the  Physical  Exploration  of  the  Chest  and 
the  Diagnosis  of  Diseases  Affecting  the  Respiratory  Organs.  Second  and 
revised  edition.  In  one  handsome  octavo  volume  of  591  pages.  Cloth,  $4.50. 

Phthisis:  Its  Morbid  Anatomy,  Etiology,  Symptomatic  Events  and 
Complications,  Fatality  and  Prognosis,  Treatment  and  Physical  Diag- 
nosis ;  In  a  series  of  Clinical  Studies.  In  one  octavo  volume  of  442  pages.  Cloth,  $3.50. 

A  Practical  Treatise  on  the  Diagnosis,  Pathology  and  Treatment  of 
Diseases  of  the  Heart.  Second  revised  and  enlarged  edition.  In  one  octavo  volume 
of  550  pages,  with  a  plate.  Cloth,  $4. 

Essays  on  Conservative  Medicine  and  Kindred  Topics.  In  one  very  hand- 
some royal  12mo.  volume  of  210  pages.  Cloth,  $1.38. 


BROWNE,  LENNOX,  F.  JR.  C.  8.,  E., 

Senior  Physician  to  the  Central  London  Throat  and  Ear  Hospital. 

A  Practical  Guide  to  Diseases  of  the  Throat  and  Nose,  including 
Associated  Affections  of  the  Ear.  New  (third)  and  enlarged  edition.  In  one 
imperial  octavo  volume  of  734  pages,  with  120  illustrations  in  color,  and  235  engravings 
on  wood.  Cloth,  $6.50. 

of  experience,  Mr.  Browne  has  found  to  be  of  the 


The  third  edition  of  Mr.  Lennox  Browne's  in- 
structive and  artistic  work  on  "  The  Throat  and 
Its  Diseases"  appears  under  the  title  of  "The 
Throat  and  Nose  and  Their  Diseases."  This 
change  has  been  rendered  desirable  by  the  ad- 
vances made  during  the  last  decade  in  rhinology. 
The  nasal  sections,  which  extend  to  upwards  of 
100  pages,  give  in  a  short  space  the  best  account 
of  the  present  position  of  rhinology  with  which 
we  are  acquainted.  The  engravings  in  this  hand- 
some volume  are  of  the  same  high  order  as  here- 
tofore, and  more  numerous  than  ever;  they  can- 
not fail  to  be  of  the  greatest  assistance  to  senior  stu- 
dents and  practitioners.  The  instruments,  either 
figured  or  described,  are  those  which,  as  the  result 


greatest  utility  in  diagnosis  and  treatment;  they  are 
most  simple,  inexpensive  and  easily  kept  aseptic — 
points  of  much  importance.  We  have  on  a  former 
occasion  eulogised  the  beautiful  and  typical  col- 
ored plates  drawn  on  stone  by  the  author-artist 
himself,  and  forming  in  themselves  a  valuable 
and  instructive  atlas,  the  equal  of  which  is  not  to 
be  found  in  any  modern  work,  treating  of  these 
subjects.  Mr.  Lennox  Browne  is  to  congratulated 
on  having  produced  the  best  practical  text-book 
on  diseases  of  the  throat  and  nose  extant.  We 
are  glad  to  learn  that  it  is  being  translated  into 
French  and  German.—  The  Provincial  Medical 
Journal,  August  1, 1890. 


BY  THE  SAME  A  UTHOR. 

Koch's  Remedy  in  Relation  to  Throat  Consumption.  In  one  octavo 
volume  of  121  pages,  with  45  illustrations,  4  of  which  are  colored,  and  17  charts. 
Cloth,  $1.50.  Just  ready. 

SEILER,  CAUL,  M.  D., 

Lecturer  on  Laryngoscopy  in  the  University  of  Pennsylvania. 

A  Handbook  of  Diagnosis  and  Treatment  of  Diseases  of  the  Throat, 
Nose  and  Naso-Pharynx.  New  (third)  edition.  In  one  handsome  royal  12mo. 
volume  of  373  pages,  with  101  illustrations  and  2  colored  plates.  Cloth,  $2.25. 

of  topics  and  methods.  The  book  deserves  a  large 
sale,  especially  among  general  practitioners— Chi- 
cago Medical  Journal  and  Examiner^  April,  1889. 


Few  medical  writers  surpass  this  author  in 
ability  to  make  his  meaning  perfectly  clear  in  a 
few  words,  and  in  discrimination  in  selection,  both 


COHEN,  J.  8OLI8,  M.  D., 

Lecturer  on  Laryngoscopy  and  Diseases  of  the  Throat  and  Chest  in  the  Jefferson  Medical  College. 

Diseases  of  the  Throat  and  Nasal  Passages.  A  Guide  to  the  Diagnosis  and 
Treatment  of  Affections  of  the  Pharynx,  (Esophagus,  Trachea,  Larynx  and  Nares.  Third 
edition,  thoroughly  revised  and  rewritten,  with  a  large  number  of  new  illustrations.  In 
one  very  handsome  octavo  volume.  Preparing. 

GROSS,  S.  JD.,  M.D.,  LL.D.,  D.C.L.  Oxon.,  LL.D.  Cantab. 

A  Practical  Treatise  on  Foreign  Bodies  in  the  Air-passages.    In  one 

octavo  volume  of  452  pages,  with  59  illustrations.    Cloth,  $2.75. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Nerv.  and  Meiit.  Dis.,  etc.     19 


KOSS,  JAMES,  M.D.,  F.K.C.P.,  LL.I>., 

Senior  Assistant  Physician  to  the  Manchester  Royal  Infirmary. 

A  Handbook  on  Diseases  of  the  Nervous   System.     In 

volume  of  725  pages,  with  184  illustrations.     Cloth,  $4.50 ;  leather,  $5.50. 

The  book  before  us  is  entitled  to  the  highest 
consideration;  it  is  painstaking,  scientific  and 
exceedingly  comprehensive. — New  York  Medical 
Journal,  July  10, 1886. 

The  author  has  rendered  a  great  service  to  the 
profession  by  condensing  into  one  volume  the 
principal  facts  pertaining  to  neurology  and  nerv- 
ous diseases  as  understood  at  the  present  time, 
and  he  has  succeeded  in  producing  a  work  at  once 
brief  and  practical  yet  scientific,  without  entering 
into  the  discussion  of  theorists,  or  burdening  the 
mind  with  mooted  questions.— Pacific  Medical  and 
Surgical  Journal  and  Western  Lanfet,  May,  1886. 


HTUiCw*  «/wt*7  MUtt/  iwtu.    rrcoc/or  r*  -uurc<1  oc/,  aftajTj  AOOU. 

This  admirable  work  is  intended  for  students  of 
medicine  and  for  such  medical  men  as  have  no  time 


one  octavo 


for  lengthy  treatises.  In  the  present  instance  the 
duty  of  arranging  the  vast  store  of  material  at  the 
disposal  of  the  author,  and  of  abridging  the  de- 
scription of  the  different  aspects  of  nervous  dis- 
eases, has  been  performed  with  singular  skill  and 
the  result  is  a  concise  and  philosophical  guide  to 
the  department  of  medicine  of  which  it  treats. 
Dr.  Ross  holds  such  a  high  scientific  position  that 
any  writings  which  bear  his  name  are  naturally 
expected  to  have  the  impress  of  a  powerful  intel- 
lect. In  every  part  this  handbook  merits  the 
highest  praise,  and  will  no  doubt  be  found  of  the 
greatest  value  to  the  student  as  well  as  to  the  prac- 


greatest  vaiue  10  me  siuaent  as  well  as  to  tne  p 
titioner.— Edinburgh  Medical  Journal,  Jan.  1887. 


HAMILTON,  ALLAN  McLANE,  M.  D., 

Attending  Physician  at  the  Hospital  for  Epileptics  and  Paralytics,  BlackuoelVa  Island,  N.  Y. 
Nervous  Diseases ;  Their  Description  and  Treatment.    Second  edition,  thoroughly 
revised  and  rewritten.   In  one  octavo  volume  of  598  pages,  with  72  illustrations.    Cloth,  $4. 
When  the  first  edition  of  this  good  bookappeared    characterized  this  book  as  the  best  of  its  kind  in 
we  gave  it  our  emphatic  endorsement,  and  the 
present  edition  enhances  our  appreciation  of  the 
book  and  its  author  as  a  safe  guide  to  students  of 
clinical  neurology.     One  of  the  best  and  most 
critical  of  English  neurological  journals,  Brain,  has 


any  language,  which  is  a  handsome  endorsement 
from  an  exalted  source.  The  improvements  in  the 
new  edition,  and  the  additions  to  it,  will  justify  its 
purchase  even  by  those  who  possess  the  old.— 
Alienist  and  Neurologist,  April,  1882. 


TVKE,  DANIEL  HACK,  M.  D., 

Joint  Author  of  The  Manual  of  Psychological  Medicine,  etc. 

Illustrations  of  the  Influence  of  the  Mind  upon  the  Body  in  Health 
and  Disease.  Designed  to  elucidate  the  Action  of  the  Imagination.  New  edition. 
Thoroughly  revised  and  rewritten.  In  one  8vo.  vol.  of  467  pp.,  with  2  col.  plates.  Cloth,  $3. 

It  is  impossible  to  peruse  these  interesting  chap- 
ters without  being  convinced  of  the  author's  per- 
fect sincerity,  impartiality,  and  thorough  mental 
grasp.  Dr.  Tuke  has  exhibited  the  requisite 
amount  of  scientific  address  on  all  occasions,  and 


the  more  intricate  the  phenomena  the  more  firmly 
has  he  adhered  to  a  physiological  and  rational 


method  of  interpretation.  Guided  by  an  enlight- 
ened deduction,  the  author  has  reclaimed  for 
science  a  most  interesting  domain  in  psychology 
previously  abandoned  to  charlatans  and  empirics. 
This  book,  well  conceived  and  well  written,  must 
commend  itself  to  every  thoughtful  understand- 
ing.— New  York  Medical  Journal,  September  6, 1884. 


GRAY,  LANDON  CARTER,  M.D., 

Professor  of  Diseases  of  the  Mind  and  Nervous  System  in  the  New  York  Polyclinic. 

A  Practical  Treatise  on  Diseases  of  the  Nervous  System. 
CLOUSTON,  THOMAS  8.,  M.  D.,  F.  R.  C.  P.,  L.  R.  C.  S., 

Lecturer  on  Mental  Diseases  in  the  University  of  Edinburgh. 

Clinical  Lectures  on  Mental  Diseases.  With  an  Appendix,  containing  an 
Abstract  of  the  Statutes  of  the  United  States  and  of  the  Several  States  and  Territories  re- 
lating to  the  Custody  of  the  Insane.  By  CHARLES  F.  FOLSOM,  M.  D.,  Assistant  Professor 
of  Mental  Diseases,  Med.  Dep.  of  Harvard  Univ.  In  one  handsome  octavo  volume  of  541 
pages,  with  eight  lithographic  plates,  four  of  which  are  beautifully  colored.  Cloth,  $4. 


the  general  practitioner  in  guiding  him  to  a  diag- 
nosis and  indicating  the  treatment,  especially  in 
many  obscure  and  doubtful  cases  of  mental  dis- 
ease. To  the  American  reader  Dr.  Folsom's  Ap- 
pendix adds  greatly  to  the  value  of  the  work,  and 
will  nuke  it  a  desirable  addition  to  every  library. 
— American  Psychological  Journal,  July,  1884. 


The  practitioner  as  well  as  the  student  will  ac- 
cept the  plain,  practical  teaching  of  the  author  as  a 
forward  step  in  the  literature  of  insanity.  It  is 
refreshing  to  find  a  physician  of  Dr.  Clouston's 
experience  and  high  reputation  giving  the  bed- 
side notes  upon  which  his  experience  has  been 
founded  and  his  mature  judgment  established. 
Such  clinical  observations  cannot  but  be  useful  to 

ftalTDr.  Folsom's  Abstract  may  also  be  obtained  separately  in  one  octavo  volume  of 
108  pages.    Cloth,  $1.50.     

SAVAGE,  GEORGE  H.,  M.  D., 

Lecturer  on  Mental  Diseases  at  Guy's  Hospital,  London. 

Insanity  and  Allied  Neuroses,  Practical  and  Clinical.     In  one  12mo.  vol. 
of  551  pages,  with  18  illus.     Cloth,  $2.00.    See  Series  of  Clinical  Manuals,  page  31. 

As  a  handbook,  a  guide  to  the  practitioner  and 
student,  the  book  fulfils  an  admirable  purpose. 
The  many  forms  of  insanity  are  described  with 
characteristic  clearness,  the  illustrative  ca; 


carefully  selected,  and  as  regards  treatment  sound 
common  sense  is  everywhere  apparent.  Dr.  Sav- 
age has  written  an  excellent  manual  for  the  prac- 
titioner and  student.— Amer.  Jour,  oflnsan.,  Apr.'SS. 


PLAYFAIH,  W.  S.,  M.  D.,  F.  R.  C.  JP. 

The  Systematic  Treatment  of  Nerve  Prostration  and  Hysteria. 

one  handsome  small  12mo.  volume  of  97  pages.     Cloth,  $1.00. 


In 


BLANDFORD  ON  INSANITY  AND  ITS  TREAT- 
MENT. Lectures  on  the  Treatment,  Medical 
and  Legal,  of  Insane  Patients.  In  one  very  hand- 
some octavo  volume. 


JONES'  CLINICAL  OBSERVATIONS  ON  FUNC- 
TIONAL NERVOUS  DISORDERS.  Second 
American  Edition.  In  one  handsome  octavo 
volume  of  340  pages.  Cloth,  $3.25. 


20 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Surgery 


ROBERTS,  JO  ELN  B.,  M.  !>., 

Professor  of  Anatomy  and  Surgery  in  the  Philadelphia  Policlinic.  Professor  of  the  Principles  and 
Practice  of  Surgery  in  the  Woman's  Medical  College  of  Pennsylvania.  Lecturer  in  Anatomy  in  the  Univer- 
sity of  Pennsylvania. 

The  Principles  and  Practice  of  Modern  Surgery.    For  the  use  of  Students 
and  Practitioners  of  Medicine  and  Surgery.     In  one  very  handsome  octavo  volume  of  780 


pciopii^tiii'.y ,     v3Uij<aLiv;v3      AVO      vaiuu     <*o     a     BI*U%AQUV  a 

manual.  The  fact  that  this  work  is  eminently 
practical  cannot  be  too  strongly  emphasized.  It 
is  modern,  and  as  its  teaching  is  that  generally 
accepted  and  such  that  affords  little  opportunity 
for  discussion,  it  will  be  lasting.  It  is  clear  and 
concise,  yet  full.  The  book  is  entitled  to  a  place 


Just  ready. 

in  modern  surgical  literature.- 
Jan.  1891. 


pages,  with  501  illustrations.    Cloth,  $4.50;  leather,  $5.50. 

In  this  work  the  author  has  endeavored  to  give 
to  the  profession  in  a  condensed  form  the  doctrines 
and  procedures  of  Modern  Surgery.  He  has  made 
it  a  work  devoted  more  especially  to  the  practice 
than  to  the  theory  of  surgery.  His  own  large 
experience  has  added  many  valuable  features  to 
the  work.  It  contains  many  practical  points  in 
diagnosis,  which  render  it  the  more  valuable  to 
the  practitioner;  and  the  systematization  which 
pervades  the  whole  work,  together  with  its 
perspicuity,  enhance  its  value  as  a  student's 


•Annals  of  Surgery, 


This  work  is  a  very  comprehensive  manual  upon 
general  surgery,  and  will  doubtless  meet  with  a 
favorable  reception  by  the  profession.  It  ha«  a 
thoroughly  practical  character,  the  subjects  are 
treated  with  rare  judgment,  its  conclusions  are  in 
accord  with  those  of  the  leading  practitioners  of 
the  art,  and  its  literature  is  fully  up  to  all  the  ad- 
vanced doctrines  and  methods  of  practice  of  the 
present  day.  Its  general  arrangement  follows 


this  rule,  and  the  author  in  his  desire  to  be  con- 


practical  is  at  times  almost  dogmatic,  but 
itirely  excusable  considering  the  admira- 


cise  and 

this  is  entirely  excusable  considering  1 

ble  manner  in  which  he  has  thus  increased  the 

usefulness  of  his  work.— Medico?  Record,  Jan.  17, 

1891. 


ASHJBTURST,  JOHN,  Jr.,  M.  !>., 

Barton  Prof,  of  Surgery  and  Clin.  Surgery  in  Univ.  of  Penna.t  Surgeon  to  the  Penna.  Hosp.,  etc. 

The  Principles  and  Practice  of  Surgery.  New  (fifth)  edition,  enlarged 
and  thoroughly  revised.  In  one  large  and  handsome  octavo  volume  of  1144  pages,  with 
642  illustrations.  Cloth,  $6 ;  leather,  $7. 

This  is  one  of  the  most  popular  and  useful  oi 
the  many  well-known  treatises  on  general  surgery. 
It  furnishes  in  a  concise  manner  a  clear  and 


A  complete  and  most  excellent  work  on  surgery. 
It  is  only  necessary  to  examine  it  to  see  at  once 
its  excellence  and  real  merit  either  as  text-book 
for  the  student  or  a  guide  for  the  general  practi 


tioner.  It  fully  considers  in  detail  every  surgical 
injury  and  disease  to  which  the  body  is  liable,  and 
every  advance  in  surgery  worth  noting  is  to  be 
found  in  its  proper  place.  It  is  unquestionably  the 
best  and  most  complete  single  volume  on  surgery, 
in  the  English  language,  and  cannot  but  receive 
that  continued  appreciation  which  its  merits  justly 
demand. — Southern  Practitioner,  Feb.  1890. 


comprehensive  description  of  the  modes  of  prac- 
tice now  generally  employed  in  the  treatment  of 
surgical  affections,  with  a  plain  exposition  of  the 
principles  on  which  those  modes  of  practice  are 
based.  The  entire  work  has  been  carefully  revised, 
and  a  number  of  new  illustrations  introduced 
that  greatly  enhance  the  value  of  the  book. — 
Cincinnati  Lancet-Clinic,  Dec.  14, 1889. 


DRUITT,  ROBERT,  M.  R.  C.  S.,  etc. 

Manual  of  Modern  Surgery.  Twelfth  edition,  thoroughly  revised  by  STAN- 
LEY BOYD,  M.  B.,  B.  S.,  F.  R.  C.  S.  In  one  8vo.  volume  of  965  pages,  with  373  illustra- 
tions. Cloth,  $4 ;  leather,  $5. 


It  is  essentially  a  new  book,  rewritten  from  be- 
ginning to  end.  The  editor  has  brought  his  work 
up  to  the  latest  date,  and  nearly  every  subject  on 
which  the  student  and  practitioner  would  desire 
to  consult  a  surgical  volume,  has  found  its  place 
here.  The  volume  closes  with  about  twenty  pages 
of  formula  covering  a  broad  range  of  practical 
therapeutics.  The  student  will  find  that  the  new 
Druitt  is  to  this  generation  what  the  old  one  was 
to  the  former,  and  no  higher  praise  need  be 
accorded  to  any  volume. — North  Carolina  Medical 
Journal,  October,  1887. 


Druitt's  Surgery  has  been  an  exceedingly  popu- 
lar work  in  the  profession.  It  is  stated  that  50,000 
copies  have  been  sold  in  England,  while  in  the 
United  States,  ever  since  its  first  issue,  it  has  been 
used  as  a  text-book  to  a  very  large  extent.  Dur- 
ing the  late  war  in  this  country  it  was  so  highly 
appreciated  that  a  copy  was  issued  by  the  Govern- 
ment to  each  surgeon.  The  present  edition,  while 
it  has  the  same  features  peculiar  to  the  work  at 
first,  embodies  all  recent  discoveries  in  surgery, 
and  is  fully  up  to  the  times.— Cincinnati  Medical 
News,  September,  1887. 


GAJSTT,  FREDERICK  JAMES,  F.  R.  C.  S., 

Senior  Surgeon  to  the  Royal  Free  Hospital,  London. 

The  Student's  Surgery.    A  Multum  in  Parvo.     In  one  square  octavo  volume 
of  848  pages,  with  159  engravings.     Cloth,  $3.75. 

GROSS,  S.  D.,  M.  !>.,  LL.  !>.,  D.  C.  L.  Oxon.,  LL.  D. 
Cantab., 

Emeritus  Professor  of  Surgery  in  the  Jefferson  Medical  College  of  Philadelphia. 
A  System  of  Surgery :    Pathological,   Diagnostic,  Therapeutic  and  Operative. 
Sixth  edition,  thoroughly  revised  and  greatly  improved.      In  two  large  and  beautifully 
printed  imperial  octavo  volumes  containing  2382  pages,  illustrated  by  1623  engravings. 
Strongly  bound  in  leather,  raised  bands,  $15. 

BALL,  CHARLES  B.,  M.  Ch.,  Dub.,  F.  R.  C.  S.,  E., 

Surgeon  and  Teacher  at  Sir  P.  Dun's  Hospital,  Dublin. 

Diseases  of  the  Rectum  and  Anus.    In    one  12mo.  volume  of  417  pp., 
with  54  cuts,  and  4  colored  plates      Cloth,  $2.25.     See  Series  of  Clinical  Manuals  31. 

GIBNEY,  V.  P.,  M.D., 

Surgeon  to  the  Orthopaedic  Hospital,  New  York,  etc. 

Orthopaedic  Surgery.    For  the  use  of  Practitioners  and  Students.    In  one  hand- 
some octavo  volume,  profusely  illustrated.     Preparing. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Surgery. 


21 


ERICHSEN,  JOHN  F.,  F.  R.  S.,  F.  M.  C.  8., 

Professor  of  Surgery  in  University  College,  London,  etc. 

The  Science  and  Art  of  Surgery ;  Being  a  Treatise  on  Surgical  Injuries,  Dis- 
5  and  Operations.  From  the  eighth  and  enlarged  English  edition.  In  two  large  and 
*:*,i  _*„_  volumes  of  2316  pages,  illustrated  with  984  engravings  on  wood. 

marked  the  progress  of  surgery  during  the  last 
decade  has  been  omitted.  The  illustrations  are 
many  and  executed  in  the  highest  style  of  art. 
—Lrmisvilte  Medical  News,  Feb.  14, 1885. 


beautiful    octavo 

Cloth,  $9;  leather,  raised  bands,  $11. 

We  have  always  regarded   "The  Science  and 
Art  of  Surgery"  as   one  of  the  best  surgical  text- 


books  in 


nglish  language,  and  this  eighth 


edition  only  confirms  our  previous  opinion.  We 
take  great  pleasure  in  cordially  commending  it  to 
our  readers.— The  Medical  News,  April  11, 1885. 

For  many  years  this  classic  work  has  been 
made  by  preference  of  teachers  the  principal 
text-book  on  surgery  for  medical  students,  while 
through  translations  into  the  leading  continental 
languages  it  may  be  said  to  guide  the  surgical 
teachings  of  the  civilized  world.  No  excellence 
of  the  former  edition  has  been  dropped  and  no 
discovery,  device  or  improvement  which  has 


We  cannot  speak  too  highly  of  this  excellent 
work.  It  represents  the  most  advanced  and  settled 
views  in  regard  to  the  science  of  surgery,  and  will 
ever  be  found  a  faithful  guide  and  counsellor  in 
practice.— Canada  Lancet,  May,  1885. 

It  appears  simultaneously  in  England,  America, 
Spain  and  Italy,  and  is  too  well  known  as  a  safe 
guide  and  familiar  friend  to  need  further  com- 
ment.*— New  York  Medical  Journal,  March  28, 1885* 


BRYANT,  THOMAS,  F.  JR.  C.  S., 

Surgeon  and  Lecturer  on  Surgery  at  Quy's  Hospital,  London. 

The  Practice  of  Surgery.  Fourth  American  from  the  fourth  and  revised  Eng- 
lish edition.  In  one  large  and  very  handsome  imperial  octavo  volume  of  1040  pages,  with 
727  illustrations.  Cloth,  $6.50;  leather,  $7.50. 

enable  the  busy  practitioner  to  review  any  subject 
in  every-day  practice  in  a  short  time.    No  time  is 


The  fourth  edition  of  this  work  is  fully  abreast 
of  the  times.  The  author  handles  his  subjects 
with  that  degree  of  judgment  and  skill  which  is 
attained  by  years  of  patient  toil  and  varied  ex- 
perience. The  present  edition  is  a  thorough  re- 
vision of  those  which  preceded  it,  with  much  new 
matter  added.  His  diction  is  so  graceful  and 
logical,  and  his  explanations  are  so  lucid,  as  to 
place  the  work  among  the  highest  order  of  text- 
cooks  for  the  medical  student.  Almost  every 
topic  in  surgery  is  presented  in  such  a  form  as  to 


lost  with  useless  theories  or  superfluous  verbiage. 
In  short,  the  work  is  eminently  clear,  logical  and 
practical.— Chicago  Medical  Journal  and  Examiner, 
April.  1886. 

This  book  is  essentially  what  it  purports  to  be, 
viz.:  a  manual  for  the  practice  of  surgery.  It  is 
peculiarly  well  fitted  for  the  student  or  busy  general 
practitioner.—  The  Medical  News,  August  15, 1885. 


TREVES,  FREDERICK,  F.  R.  C.  S., 

Hunterian  Professor  at  the  Royal  College  of  Surgeons  of  England. 

A  Manual  Of  Surgery.  In  Treatises  by  Various  Authois.  In  three  12mo. 
volumes,  containing  1866  pages,  with  213  engravings.  Price  per  volume,  cloth,  $2.  See 
Students'  Series  of  Manuals,  page  31. 

We  have  here  the  opinions  of  thirty-three 
authors,  in  an  encyclopaedic  form  for  easy  and 
ready  reference.  The  three  volumes  embrace 


every  variety  of  surgical  affections  likely  to  be 
met  with,  the  paragraphs  are  short  and  pithy,  and 


the  salient  points  and  the  beginnings  of  new  sub- 
jects are  always  printed  in  extra-heavy  type,  so 
that  a  person  may  find  whatever  information  he 
may  be  in  need  of  at  a  moment's  glance. — Cin- 
cinnati Lancet-Clinic,  August  21, 1886. 


HOLMES,  TIMOTHY,  M.  A., 

Surgeon  and  Lecturer  on  Surgery  at  St,  George's  Hospital,  London. 

A  System  of  Surgery  ;  Theoretical  and  Practical.  IN  TEEATISES  BY 
VARIOUS  AUTHORS.  AMERICAN  EDITION,  THOROUGHLY  REVISED  AND  RE-EDITEI> 
by  JOHN  H.  PACKARD,  M.  D.,  Surgeon  to  the  Episcopal  and  St.  Joseph's  Hospitals, 
Philadelphia,  assisted  by  a  corps  of  thirty-three  of  the  most  eminent  American  surgeons. 
In  three  large  imperial  octavo  volumes  containing  3137  double-  columned  pages,  with 
979  illustrations  on  wood  and  13  lithographic  plates,  beautifully  colored.  Price  per 
set,  cloth,  $18.00  ;  leather,  $21.00.  Sold  only  by  subscription. 

MARSH,  HOWARD,  F.  M.  C.  S., 

Senior  Assistant  Surgeon  to  and  Lecturer  on  Anatomy  at  St.  Bartholomew's  Hospital,  London. 

Diseases  of  the  Joints.  In  one  12mo.  volume  of  468  pages,  with  64  woodcute 
and  a  colored  plate.  Cloth,  $2.00.  See  Series  of  Clinical.  Manuals,  page  31. 


BUTLIN 


F.  M.  C.  8., 


, 

Assistant  Surgeon  to  St.  Bartholomew's  Hospital,  London. 
Diseases    Of   the   Tongue.     In  one  12mo.  volume  of  456  pages,  with  8  colored 
plates  and  3  woodcuts.    Cloth,  $3.50.     See  Series  of  Clinical  Manuals,  page  31. 

TREVES,  FREDERICK,  F.  H.  C.  S., 

Surgeon  to  and  Lecturer  on  Surgery  at  the  London  Hospital. 

Intestinal  Obstruction.    In  one  pocket-size  12mo.  volume  of  522  pages,  with  60 
illustrations.  Limp  cloth,  blue  edges,  $2.00.    See  Series  of  Clinical  Manuals,  page  31. 

GOULD,  A.  PEAItCE,  M.  S.,  M.  B.,  I.  JK.  C.  S,, 

Assistant  Surgeon  to  Middlesex  Hospital. 

Elements  of  Surgical  Diagnosis.    In  one  pocket-size  12mo.  volume  of  589 
pages.     Cloth,  $2.00.     See  Students'  Series  of  Manuals,  page  31. 


PIRRIE'S  PRINCIPLES  AND  PRACTICE  OF 
SURGERY.  Edited  by  JOHN  NBILL,  M.  D.  In 
one  8vo.  vol.  of  784  pp.  with  316  illus.  Cloth,  $3.75. 

MILLER'S  PRINCIPLES  OF  SURGERY.  Fourth 
American  from  the  third  Edinburgh  edition.  In 


one  8vo.  vol.  of  638  pages,  with  340  illustrations. 
Cloth,  $3.75. 

MILLER'S  PRACTICE  OF  SURGERY.  Fourth 
and  revised  American  edition.  In  one  large  8vo. 
vol.  of  682  pp.,  with  364  illustrations.  Cloth,  $3.75. 


22      LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Surgery,  Frac.,  Disloc. 


SMITH,  STEPHEN,  M.  D., 

Professor  of  Clinical  Surgery  in  the  University  of  the  City  of  New  York. 

The  Principles  and  Practice  of  Operative  Surgery.  New  (second)  and 
thoroughly  revised  edition.  In  one  very  handsome  octavo  volume  of  892  pages,  with 
1005  illustrations.  Cloth,  $400;  leather,  $5.00. 


\J\J*J     &JL1.U0V4.CMM.VUQC  ^/AWUil,     ^  1:-  \J\J  ,       &VCWVUVJ.J    <|>U 

This  excellent  and  very  valuable  book  is  one  of 
the  most  satisfactory  works  on  modern  operative 
surgery  yet  published.  Its  author  and  publisher 
have  spared  no  pains  to  make  it  as  far  as  possible 
an  ideal,  and  their  efforts  have  given  it  a  position 
prominent  among  the  recent  works  in  this  depart- 
ment of  surgery.  The  book  is  a  compendium  for 
the  modern  surgeon.  The  present,  the  only  revised 
edition  since  1879,  presents  many  changes  from 
the  original  manual.  The  volume  is  much  en- 
larged, and  the  text  has  been  thoroughly  revised, 
so  as  to  give  the  most  improved  methods  in  asep- 


tic surgery,  and  the  latest  instruments  known  for 
operative  work.  It  can  be  truly  said  that  as  a  hand- 
book for  the  student,  a  companion  for  the  surgeon, 
and  even  as  a  book  of  reference  for  the  physician 
not  especially  engaged  in  the  practice  or  surgery, 
this  volume  will  long  hold  a  most  conspicuous 
place,  and  seldom  willits  readers,  no  matter  how 
unusual  the  subject,  consult  its  pages  in  vain.  Its 
compact  form,  excellent  print,  numerous  illustra- 
tions, and  especially  its  decidedly  practical  char- 
acter, all  combine  to  commend  it.— Boston  Medical 
and  Surgical  Journal,  May  10, 1888. 


HOLMES,  TIMOTHY,  M.  A., 

Surgeon  and  Lecturer  on  Surgery  at  St.  George's  Hospital,  London. 

A  Treatise  on  Surgery;  Its  Principles  and  Practice.  New  American 
from  the  fifth  English  edition,  edited  by  T.  PICKERING  PICK,  F.  R.  C.  S.,  Surgeon  and 
Lecturer  on  Surgery  at  St.  George's  Hospital,  London,  In  one  octavo  volume  of  997 
pages,  with  428  illustrations.  Cloth,  $6 ;  leather,  $7. 

To  the  younger  members  of  the  profession  and 
to  others  not  acquainted  with  the  book  and  its 
merits,  we  take  pleasure  in  recommending  it  as  a 


surgery   complete,   thorough,  well-written, 
illustrated,  modern,   a  work  sufficiently  volumi- 
nous for  the  surgeon  specialist,  adequately  concise 


for  the  general  practitioner,  teaching  those  things 
that  are  necessary  to  be  known  for  the  successful 
prosecution  of  the  physician's  career,  imparting 
nothing  that  in  our  present  knowledge  is  consid- 
ered unsafe,  unscientific  or  inexpedient.— Pacific 
Medical  Journal,  July,  1889. 


HAMILTON,  FRANK  H.,  M.  &.,  LL.  IX, 

Surgeon  to  Bellevue  Hospital,  New  York. 

A  Practical  Treatise  on  Fractures  and  Dislocations.  New  (8th)  edi- 
tion, revised  and  edited  by  STEPHEN  SMITH,  A.  M.,  M.  D.,  Professor  of  Clinical  Surgery 
in  the  University  of  the  City  of  New  York.  In  one  very  handsome  octavo  volume  of  832 
pages,  with  507  illustrations.  Cloth,  $5.50 ;  leather,  $6.50.  Just  ready. 

It  has  received  the  highest  endorsement  that  a  |  tioner,  in  his  character  as  a  surgeon,  is  most  called 
work  upon  a  department  of  surgery  can  possibly  !  upon  to  treat.  They  form  a  part  of  surgery  that 
receive.  It  is  used  as  a' text-book  in  every  medi  j  he  cannot  avoid  taking  charge  of.  Under  the 

circumstances,  therefore,  he  needs  all  the  aid  he 
can  secure.  But  what  better  assistance  can  he 
seek  than  a  work  that  is  devoted  exclusively  to 
treating  fractures  and  dislocations,  and  conse- 
quently contains  full  information,  in  plain  lan- 
guage, for  the  management  of  every  emergency 
that  is  likely  to  be  met  with  in  such  injuries? 
The  country  is  filled  with  railroads  and  manufac- 
tories where  accidents  are  constantly  occurring, 
and  to  which  general  practitioners,  and  not  dis- 
tinguished surgeons,  are  constantly  liable  to  be 
called.  We  consider  that  the  work  before  us 
should  be  in  the  library  of  every  practitioner.— 
Cincinnati  Medical  News,  February,  1891. 


cal  college  of  this  country,  and  the  publishers 
have  been  called  upon  to  print  eight  editions  of  it. 
What  more  can  be  said  in  commendation  of  it? 
It  has  been  said  with  truth  that  it  is  doubtful  if 
any  surgical  work  has  appeared  during  the  last 
half  century  which  more  completely  filled  the 
place  for  which  it  was  designed.  As  Dr.  Smith 
says,  its  great  merits  appear  most  conspicuously 
in  its  clear,  concise,  and  yet  comprehensive  state- 
ment of  principles,  which  renders  it  an  admirable 
text- book  for  teacher  and  pupil,  and  in  its  wealth 
of  clinical  materials,  which  adapts  it  to  the  daily 
necessities  of  the  practitioner.  Fractures  and 
dislocations  are  injuries  which  the  general  practi- 


STIMSON,  LEWIS  A.,  B.  A.,  M.  &., 

Surgeon  to  the  Presbyterian  and  Bellevue  Hospitals,  Professor  of  Clinical  Surgery  in  the  Medical 


Faculty  of  Univ.  of  City  of  N.   Y.,  Corresponding  Member  of  the  Societe  de  Chirurgie  of  Paris. 

A  Manual  of  Operative  Surgery.    New  (second)  edition.    In  one  - 
some  royal  12mo.  volume  of  503  pages,  with  342  illustrations.    Cloth,  $2.50. 


There  is  always  room  for  a  good  book,  so  that 
while  many  works  on  operative  surgery  must  be 
considered  superfluous,  that  of  Dr.  Stimson  has 
held  its  own.  The  author  knows  the  difficult  art 
of  condensation.  Thus  the  manual  serves  as  a 
work  of  reference,  and  at  the  same  time  as  a 
handy  guide.  It  teaches  what  it  professes,  the 
steps  of  operations.  In  this  edition  Dr.  Stimson 
has  sought  to  indicate  the  changes  that  have  been 


effected  in  operative  methods  and  procedures  by 
the  antiseptic  system,  and  has  added  an  account 
of  many  new  operations  and  variations  in  the 
steps  of  older  operations.  We  do  not  desire  to 
extol  this  manual  above  many  excellent  standard 
British  publications  of  the  same  class,  still  we  be- 
lieve that  it  contains  much  that  is  worthy  of  imi- 
tation.— British  Medical  Journal,  Jan.  22,  1887. 


By  the  same  Author. 

A  Treatise  on  Fractures  and  Dislocations.  In  two  handsome  octavo  vol- 
umes. Vol.  I.,  FRACTURES,  582  pages,  360  beautiful  illustrations.  Vol.  II.,  DISLOCA- 
TIONS, 540  pages,  with  163  illustrations.  Complete  work,  cloth,  $5.50 ;  leather,  $7.50. 
Either  volume  separately,  cloth,  $3.00 ;  leather,  $4.00. 

The  appearance  of  the  second  volume  marks  the  of  Dislocations  as  it  is  taught  and  practised  by  the 
completion  of  the  author's  original  plan  ofprepar-  most  eminent  surgeons  of  the  present  time.  Ccn- 
ing  a  work  which  should  present  in  the  fullest  taining  the  results  of  such  extended  researches  it 

must  for  a  long  time  be  regarded  as  an  authority 
on  all  subjects  pertaining  to  dislocations.  Every 
practitioner  of  surgery  will  feel  it  incumbent  on 
him  to  have  it  for  constant  reference.— Cincinnati 
Medical  News,  May,  1888. 


manner  all  that  is  known  on  the  cognate  subjects 
of  Fractures  and  Dislocations.  The  volume  on 
Fractures  assumed  at  once  the  position  of  authority 
on  the  subject,  and  its  companion  on  Dislocations 
will  no  doubt  be  similarly  received.  The  closing 
volume  of  Dr.  Stimson's  work  exhibits  the  surgery 


PICK,  T.  PICKERING,  F.  It.  C.  S., 

Surgeon  to  and  Lecturer  on  Surgery  at  St.  George's  Hospital,  London. 

Fractures  and  Dislocations.     In  one  12mo.  volume  of  530  pages,  with  93 
illustrations.    Limp  cloth,  $2.00.    See  Series  of  Clinical  Manuals,  page  31. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Otol.,  Ophtlial. 


BURNETT,  CHARLES  H.,  A.  M.9  M.  Z>., 

Professor  of  Otology  in  the  Philadelphia  Polyclinic;  President  of  the  American  Otological  Society. 

The  Ear,  Its  Anatomy,  Physiology  and  Diseases.  A  Practical  Treatise 
for  the  use  of  Medical  Students  and  Practitioners.  Second  edition.  In  one  handsome 
octavo  volume  of  580  pages,  with  107  illustrations.  Cloth,  $4.00 ;  leather,  $5.00. 


We  note  with  pleasure  the  appearance  of  a  second 
edition  of  this  valuable  work.  When  it  first  came 
out  it  was  accepted  by  the  profession  as  one  of 
the  standard  works  on  modern  aural  surgery  in 
the  English  language;  and  in  his  second  edition 
Dr.  Burnett  has  fully  maintained  his  reputation, 
for  the  book  is  replete  with  valuable  information 
and  suggestions.  The  revision  has  been  carefully 


carried  out,  and  much  new  matter  added.  Dr. 
Burnett's  work  must  be  regarded  as  a  very  valua- 
ble contribution  to  aural  surgery,  not  only  on 
account  of  its  comprehensiveness,  but  because  it 
contains  the  results  of  the  careful  personal  observa- 
tion and  experience  of  this  eminent  aural  surgeon. 
—London  Lancet,  Feb.  21, 1885. 


BERRY,  GEORGE  A.,  M.  B.,  F.  R.  C.  S.,  Ed., 

Ophthalmic  Surgeon,  Edinburgh  Royal  Infirmary. 

Diseases  of  the  Eye.    A  Practical  Treatise  for  Students  of  Ophthalmology.    In 
one  octavo  volume  of  683  pages,  with    144    illustrations,  62  of  which  are  beautifully 
colored.    Cloth,  $7.50. 
This  newest  candidate  for  favor  among  ophthal- 


mological  students  is  designed  to  be  purely  clinical 
in  character  and  the  plan  is  well  adhered  to.  We 
have  been  forcibly  struck  by  the  rare  good  taste 
in  the  selection  of  what  is  essential  which  per- 
vades the  book.  The  author  seems  to  have  the 
uncommon  faculty  of  viewing  his  subject  as  a 
whole  and  seizing  the  salient  points  and  notj con- 
fusing his  reader— presumably  a  student  and  a 


novice— with  a  mass  of  details  with  no  key  to  their 
unravelling.  It  is  apparent  that  the  literature  of 
each  subject  has  been  gone  over  in  a  very  thor- 
ough manner.  The  fact  that  he  was  writing  a 
clinical  treatise  for  beginners  and  not  an  encyclo- 
pedia has  always  been  present  with  the  author. 
The  number  and  excellence  of  the  colored  illus- 
trations in  the  text  deserve  more  than  a  passing 
notice.— Archives  of  Ophthalmology,  Sept.  1889. 


NETTLESHIP,  EDWARD,  F.  R.  C.  S., 

Ophthalmic  Surgeon  at  St.  Thomas'  Hospital,  London.    Surgeon  to  the  Royal  London  (Moorfieldt>y 
Ophthalmic  Hospital. 

Diseases  of  the  Eye.  New  (fourth)  American  from  the  fifth  English  edition, 
thoroughly  revised.  With  a  Supplement  on  the  Detection  of  Color  Blindness,  by  WIL- 
LIAM THOMSON,  M.  D.,  Professor  of  Ophthalmology  in  the  Jefferson  Medical  College. 
In  one  12mo.  volume  of  500  pages,  with  164  illustrations,  selections  from  Snellen's  test- 
types  and  formulae,  and  a  colored  plate.  Cloth,  $2.00.  Just  ready. 


This  is  a  well-known  and  a  valuable  wons.  It 
was  primarily  intended  for  the  use  of  students, 
and  supplies  their  needs  admirably,  but  it  is  as 
useful  lor  the  practitioner,  or  indeed  more  so.  It 
does  not  presuppose  the  large  amount  of  recondite 
knowledge  to  be  present  which  seems  to  be  as- 
sumed in  some  of  our  larger  works,  is  not  tedious 
from  over-conciseness,  and  yet  covers  the  more 


important  parts  of  clinical  ophthalmology.  A 
supplement  is  made  to  the  present  edition  on  the 
practical  examination  of  railroad  employes  as  to- 
color-blindness  and  acuteness  of  vision  and  hear- 
ing. This  is  well  written,  and  contains  good 
suggestions  for  those  who  may  be  called  on  to 
make  such  examinations. — New  York  Medical 
Journal,  December  13, 1890. 


JULER,  HENRY  E*,  F.  R.  C.  S., 

Senior  Ass't  Surgeon,  Royal  Westminster  Ophthalmic  Hosp. ;  late  Clinical  Ass't,  Moorfields,  London. 

A  Handbook  of  Ophthalmic  Science  and  Practice.  Handsome  870.  vol- 
ume of  460  pages,  with  125  woodcuts,  27  colored  plates,  selections  from  Test-types  of 
Jaeger  and  Snellen,  and  Holmgren's  Color-blindness  Test.  Cloth,  $4.50 ;  leather,  $5.50. 

It  presents  to  the  student  concise  descriptions 
and  typical  illustrations  of  all  important  eye  affec- 
tions, placed  in  juxtaposition,  so  as  to  be  grasped 
at  a  glance.  Beyond  a  doubt  it  is  the  best  illus- 
trated handbook  of  ophthalmic  science  which  has 
ever  appeared.  Then,  what  is  still  better,  these 


illustrations  are  nearly  all  original.  We  have  ex- 
amined this  entire  work  with  great  care,  and  it 
represents  the  commonly  accepted  views  of  ad- 
vanced ophthalmologists.  We  can  most  heartily 
commend  this  book  to  all  medical  students,  prac- 
titioners and  specialists.— Detroit  Lancet,  Jan.  '85. 


NORRIS,  WM.  F.,  M.  D.,  and  OLIVER,  CHAS.  A.,  M.  D. 

Clin.  Prof,  of  Ophthalmology  in  Univ.  of  Pa. 

A  Text-Book  of  Ophthalmology.  In  one  octavo  volume  of  about  500  pages, 
with  illustrations.  Preparing. 

CARTER,  R.  BRTTDENELL,  &  FROST,  W.ADAMS, 

F.  R.  C.  S.,  F.  R.  C.  S., 

Ophthalmic  Surgeon  to  and  Lect.  on  Ophthal-  Ass't  Ophthalmic  Surgeon  and  Joint  Lect. 

mic  Surgery  at  St.  George's  Hospital,  London.  on  Oph.  Sur.,  St.  George's  Hosp.,  London. 

Ophthalmic  Surgery.  In  one  12mo.  volume  of  559  pages,  with  91  woodcuts, 
color-blindness  test,  test-types  and  dots  and  appendix  of  formulae.  Cloth,  $2.25.  See 
Series  of  Clinical  Manuals,  page  31. 


WELLS  ON  THE  EYE.    In  one  octavo  volume. 

LAURENCE  AND  MOON'S  HANDY  BOOK  OF 
OPHTHALMIC  SURGERY,  for  the  use  of  Prac- 
titioners. Second  edition.  In  one  octavo  vol- 
ume of  227  pages,  with  65  illus.  Cloth,  $2.75. 


LAWSON  ON  INJURIES  TO  THE  EYE,  ORBIT 
AND  EYELIDS:  Their  Immediate  and  Remote 
Effects.  In  one  octavo  volume  of  404  pages,  with 
92  illustrations.  Cloth,  $3.50. 


24    LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Urin.  Dis.,  Dentistry,  etc. 


ROBERTS,  WILLIAM,  M.  D., 

Lecturer  on  Medicine  in  the  Manchester  School  of  Medicine,  etc. 

A  Practical  Treatise  on  Urinary  and  Renal  Diseases,  including  Uri- 
nary Deposits.  Fourth  American  from  the  fourth  London  edition.  In  one  hand- 
some octavo  volume  of  609  pages,  with  81  illustrations.  Cloth,  $3.50. 

It  may  be  said  to  be  the  best  book  in  print  on  the  I  a  completeness  not  found  elsewhere  in  our  Ian- 
subject  of  which  it  treats.— The  American  Journal  I  guage  in  its  account  of  the  different  affections.— 
of  the  Medical  Sciences,  Jan.  1886.  The  Manchester  Medical  Chronicle,  July,  1885. 

The  peculiar  value  and  finish  of  the  book  are  in  The  value  of  this  treatise  as  a  guide  book  to  the 
a  measure  derived  from  its  resolute  maintenance  physician  in  daily  practice  can  hardly  be  over- 


of  a  clinical  and  practical  character.  It  is  an  un 
rivalled  exposition  of  everything  which  relates 
directly  or  indirectly  to  the  diagnosis,  prognosis 
and  treatment  of  urinary  diseases,  and 


estimated.  That  it  is  fully  up  to  the  level  of  our 
present  knowledge  is  a  fact  reflecting  great  credit 
upon  Dr.  Roberts,  who  has  a  wide  reputation  as  a 
busy  practitioner. — Medical  Record,  July  31,  1886. 


CHARLES  W.,  M.  D.,  Chicago. 

Bright's  Disease  and  Allied  Affections  of  the  Kidneys.    In  one  octavo 
volume  of  288  pages,  with  illustrations.     Cloth,  $2. 

short  space  the  theories,  facts  and  treatments,  and 
going  more  fully  into  their  later  developments. 


The  object  of  this  work  is  to  "furnish  a  system- 
atic, practical  and  concise  description  of  the 
pathology  and  treatment  of  the  chief  organic 
diseases  of  the  kidney  associated  with  albuminu- 
ria,  which  shall  represent  the  most  recent  ad- 
vances in  our  knowledge  on  these  subjects  ; "  and 
this  definition  of  the  object  is  a  fair  description  of 
the  book.  The  work  is  a  useful  one,  giving  in  a 


On  treatment  the  writer  is  particularly  strong 
steering  clear  of  generalities,  and  seldom  omit- 
ting, what  text-books  usually  do,  the  unimportant 
items  which  are  all  important  to  the  general  prac- 
titioner.— The  Manchester  Medical  Chronicle,  Oct. 
1886. 


MORRIS,  HENRY,  M.  B.,  F.  R.  C.  8.9 

Surgeon  to  and  Lecturer  on  Surgery  at  Middlesex  Hospital,  London. 

Surgical  Diseases  of  the  Kidney.     In  one  12mo.  volume  of  554  pages,  with  40 
woodcuts,  and  6  colored  plates.  Limp  cloth,  $2.25.   See  Series  of  Clinical  Manuals,  page  31. 


In  this  manual  we  have  a  distinct  addition  to 
surgical  literature,  which  gives  information  not 
elsewhere  to  be  met  with  in  a  single  work.  Such 
a  book  was  distinctly  required,  and  Mr.  Morris 
has  very  diligently  and  ably  performed  the  task 


he  took  in  hand.  It  is  a  full  and  trustworthy 
book  of  reference,  both  for  students  and  prac- 
titioners in  search  of  guidance.  The  illustrations 
in  the  text  and  the  chromo-lithographs  are  beau- 
tifully executed.— The  London  Lancet,Feb.  26, 1886. 


See  Series 


LUCAS,  CLEMENT,  M.  B.,  B.  S.,  F.  R.  C.  S., 

Senior  Assistant  Surgeon  to  Guy's  Hospital,  London. 

Diseases   Of  the   Urethra.      In  one    12mo.   volume.     Preparing, 
of  Clinical  Manuals,  page  4. 

THOMPSON,  SIR  HENRY, 

Surgeon  and  Professor  of  Clinical  Surgery  to  University  College  Hospital,  London. 

Lectures  on  Diseases  of  the  Urinary  Organs.  Second  American  from  the 
third  English  edition.  In  one  8vo.  volume  of  203  pp.,  with  25  illustrations.  Cloth,  $2.25. 

By  the  Same  Author. 

On  the  Pathology  and  Treatment  of  Stricture  of  the  Urethra  and 
Urinary  Fistulse.  From  the  third  English  edition.  In  one  octavo  volume  of  359 
pages,  with  47  cuts  and  3  plates.  Cloth,  $3.50. 

THE  AMERICAN  SYSTEM  OF  DENTISTRY. 

In  Treatises  by  Various  Authors.  Edited  by  WILBUR  F.  LITCH,  M.  D., 
D.  D.  S.,  Professor  of  Prosthetic  Dentistry,  Materia  Medica  and  Therapeutics  in  the 
Pennsylvania  College  of  Dental  Surgery.  In  three  very  handsome  octavo  volumes  con- 
taining 3160  pages,  with  1863  illustrations  and  9  full-page  plates.  Per  volume,  cloth,  $6  ; 
leather,  $7 ;  half  Morocco,  gilt  top,  $8.  The  complete  work  is  now  ready.  For  sale  by 
subscription  only. 

As  an  encyclopaedia  of  Dentistry  it  has  no  su- 
perior. It  should  form  a  part  of  every  dentist's 
library,  as  the  information  it  contains  is  of  the 
greatest  value  to  all  engaged  in  the  practice  of 
dentistry.— American  Jour.  Dent.  Sci.,  Sept.  1886. 

A  grand  system,  big  enough  and  good  enough 
and  handsome  enough  for  a  monument  (which 


doubtless  it  is),  to  mark  an  epoch  in  the  history  of 
dentistry.  Dentists  will  be  satisfied  with  it  and 
proud  of  it— they  must.  It  is  sure  to  be  precisely 
what  the  student  needs  to  put  him  and  keep  him 
in  the  right  track,  while  the  profession  at  large 
will  receive  incalculable  benefit  from  it.— C  * 
graphic  Journal,  Jan.  1887. 


COLEMAN,  A.,  L.  _R.  C.  JP.,  F.  jB.  C.  S.,  Exam.  L.  &.  S., 

Senior  Dent.  Surg.  and  Lect.  on  Dent.  Surg.  at  St.  Bartholomew's  Hosp.  and  the  Dent.  Hosp.,  London. 

A  Manual  of  Dental  Surgery  and  Pathology.  Thoroughly  revised  and 
adapted  to  the  use  of  American  Students,  by  THOMAS  C.  STELLWAGEN,  M.  A.,  M.  D., 
D.  D.  S.,  Prof,  of  Physiology  in  the  Philadelphia  Dental  College.  In  one  handsome  octavo 
volume  of  412  pages,  with  331  illustrations.  Cloth,  $3.25. 

It  should  be  in  the  possession  of  every  practi- 
tioner in  this  country.  The  part  devoted  to  first 
and  second  dentition  and  irregularities  in  the  per- 
manent teeth  is  fully  worth  the  price.  In  fact, 


price  should  not  be  considered  in  purchasing  such 
a  work.  If  the  money  put  into  some  of  our  so- 
called  standard  text-books  could  be  converted  into 
such  publications  as  this,  much  good  would  result. 
— Southern  Dental  Journal,  May,  1882. 


The  author  brings  to  his  task  a  large  experience 
acquired  under  the  most  favorable  circumstances. 
There  have  been  added  to  the  volume  a  hundred 
pages  by  the  American  editor,  embodying  the 
views  of  the  leading  home  teachers  in  dental  sur- 
gery. The  work,  therefore,  may  be  regarded  as 
strictly  abreast  of  the  times,  and  as  a  very  high 
authority  on  the  subjects  of  which  it  treats.— 
American  Practitioner,  July,  1882. 


BASHAM 
Guide  to  their  Diagnosis  and  Treatment. 


ON   RENAL  DISEASES:   A  Clinical    I   one  12m o.  vol.  of  304  pages,  with  21  illustrations. 

In    I    Cloth,  $2.00. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Venereal,  Impotence. 


25 


GROSS,  SAMUEL  W.,  A.  M.,  M.  D.,  LL.  !>., 

Professor  of  the  Principles  of  Surgery  and  of  Clinical  Surgery  in  the  Jefferson  Medical  College  of  Phila. 

A  Practical  Treatise  on  Impotence,  Sterility,  and  Allied  Disorders 
Of  the  Male  Sexual  Organs.  New  (4th)  edition,  thoroughly  revised  by  F.  K, 
STURGIS,  M.  D.,  Prof,  of  Diseases  of  the  Genito- Urinary  Organs  and  of  Venereal  Diseases, 
K.  Y.  Post  Grad.  Med.  School.  In  one  very  handsome  octavo  volume  of  165  pages, 
with  18  illustrations.  Cloth,  $1.50.  Just  ready. 


Without  question  this  is  the  most  valuable  book 
ever  written  on  this  subject.  Dr.  Gross  has  devoted 
time  and  talent  to  the  study  of  these  disorders, 
with  the  result  of  immensely  increasing  our  in- 
timate knowledge  as  to  the  nature  of  the  com- 
plaints and  teaching  how  best  to  remedy  them. 
The  book  is  reliable  and  authoritative.— Pacific 
Medical  Journal,  Dec.  1890. 

It  has  been  the  aim  of  the  author  to  supply  in  a 
compact  form,  practical  and  strictly  scientific 
information  especially  adapted  to  the  wants  of  the 
general  practitioner  in  regard  to  a  class  of  common 
and  grave  disorders.  The  work  contains  very 
many  facts  in  regard  to  the  sexual  disorders  of 
men,  of  the  most  interesting  character.  We  com- 
mend the  study  of  it  to  every  professional  man, 


and  especially  to  those  engaged  in  the  general 

Sractice  of  medicine.— Cincinnati  Medical   News, 
an.  1891. 

The  work  before  us  has  become  a  standard  text- 
book on  the  subjects  of  which  it  treats.  In  the 
present  edition  the  author's  work  has  been  con- 
siderably augmented  by  Dr.  Sturgis,  whose  con- 
tributions and  views  are  to  be  seen  everywhere. 
They  contain  many  valuable  suggestions  and  are 
the  fruit  of  a  ripe  experience  which  cannot  but 
enhance  the  original  text.  The  profession  is 
quick  to  appreciate  succinct  treatises  which  are 
full  and  complete,  more  especially  when  the 
authors  are  known  to  be  worthy  of  respect  and 
confidence. — St.  Louis  Medical  and  Surgical  JournaL 
Feb.  1891. 


TAYLOR,  JB.  W.,  A.  M.,  M.  D., 

Clinical  Professor  of  Genito-Urinary  Diseases  in  the  College  of  Physicians  and  Surgeons,  New  For  At, 
Prof,  of  Venereal  and  Skin  Diseases  in  the  University  of  Vermont, 

The  Pathologjr  and  Treatment  of  Venereal  Diseases.  Including  the 
results  of  recent  investigations  upon  the  subject.  Being  the  sixth  edition  of  Bumstead 
and  Taylor.  Entirely  rewritten  by  Dr.  Taylor.  Large  8vo.  volume,  about  900  pages, 
with  about  150  engravings,  as  well  as  numerous  chromo-lithographs.  In  active  preparation. 

A  few  notices  of  the  previous  edition  are  appended. 

It  is  a  splendid  record  of  honest  labor,  wide  I  The  verdict  of  the  profession  nas  been  passed;  it 
research,  just  comparison,  careful  scrutiny  and  •  has  been  accepted  as  the  most  thorough  and  corn- 
original  experience,  which  will  always  be  held  as  j  plete  exposition  of  the  pathology  and  treatment  of 
a  high  credit  to  American  medical  literature.  This  venereal  diseases  in  the  language.  A 


is  not  only  the  best  work  in  the  English  language 
upon  the  subjects  of  which  it  treats,  but  also  one 
wnich  has  no  equal  in  other  tongues  for  its  clear, 
comprehensive  and  practical  handling  of  its 
tftemes.— Am.  Jour,  of  the  Med.  Sciences,  Jan.  1884. 
The  character  of  this  standard  work  is  so  well 
known  that  it  would  be  superfluous  here  to  pass  in 
review  its  general  or  special  points  of  excellence. 


Admirable  as  a 

model  of  clear  description,  an  exponent  of  sound 
pathological  doctrine,  and  a  guide  for  rational  and 
successful  treatment,  it  is  an  ornament  to  the  medi- 
cal literature  of  this  country.  The  additions  made 
to  the  present  edition  are  eminently  judicious, 
from  the  standpoint  of  practical  utility.— Journal  of 
Cutaneous  and  Venereal  Diseases,  Jan.  1884. 


CORNIL,  V., 

Professor  to  the  Faculty  of  Medicine  of  Paris,  and  Physician  to  the  Lourcine  Hospital. 


Specially 


Syphilis,  its  Morbid  Anatomy,  Diagnosis  and  Treatment. 

revised  by  the  Author,  and  translated  with  notes  and  additions  by  J.  HENRY  C.  SIMES, 
M.  D.,  Demonstrator  of  Pathological  Histology  in  the  Univ.  of  Pa.,  and  J.  WILLIAM 
WHITE,  M.  D.,  Lecturer  on  Venereal  Diseases,  Univ.  of  Pa.  In  one  handsome  octavo 
volume  of  461  pages,  with  84  very  beautiful  illustrations.  Cloth,  $3.75. 

The  anatomy,  the  histology,  the  pathology  and    perusal  without  the  feeling  that  his  grasp  of  the 
the  clinical  features  of  syphilis  are  represented  in    wide  and  important  subject  on  which  it  treats  is 
this  work  in  their  best,  most  practical  and  most 
instructive  form,  and  no  one  will  rise  from  its 


stronger  and  surer   one.— The  London  Practi- 
tioner, Jan.  1882. 


HUTCHINSON,  JONATHAN,  F.  K.  S.,  F.  It.  C.  8.9 

Consulting  Surgeon  to  the  London  Hospital. 

Syphilis.     In  one  12mo.  volume  of  542  pages,  with  8  chromo-lithographs.     Cloth, 
$2.25.     See  Series  of  Clinical  Manuals,  page  31. 

Those  who  have  seen  most  of  the  disease  and 
those  who  have  felt  the  real  difficulties  of  diagno- 
sis and  treatment  will  most  highly  appreciate  the 
facts  and  suggestions  which  abound  in  these 
pages.  It  is  a  worthy  and  valuable  record,  not 
only  of  Mr.  Hutchinson's  very  large  experience 


and  power  of  observation,  but  of  his  patience  and 
assiduity  in  taking  no-tes  of  his  cases  and  keep- 
ing them  in  a  form  available  for  such  excellent 
use  as  he  has  put  them  to  in  this  volume. — London. 
Medical  Record,  Nov.  12, 1887. 


GROSS,  S.  !>.,  M.  D.,  LL.  D.,  J>.  C.  L.,  etc. 

A  Practical  Treatise  on  the  Diseases,  Injuries  and  Malformations 
of  the  Urinary  Bladder,  the  Prostate  Gland  and  the  Urethra.  Third 
edition,  thoroughly  revised  by  SAMUEL  W.  GROSS,  M.  D.  In  one  octavo  volume  of  574 
pages,  with  170  illustrations.  Cloth,  $4.50. 

CULLERIER,  A.,  &  BUMSTEAD,  F.  J.,  M.D.,  LL.D., 

Surgeon  to  the  Hopital  du  Midi.         Late  Professor  of  Venereal  Diseases  in  the  College  of  Physicians 

and  Surgeons,  New  York. 

An  Atlas  of  Venereal  Diseases.  Translated  and  edited  by  FREEMAN  J.  BUM- 
STEAD,  M.  D.  In  one  imperial  4to.  volume  of  328  pages,  double-columns,  with  26  plates, 
containing  about  150  figures,  beautifully  colored,  many  of  them  the  size  of  life.  Strongly 
bound  in  cloth,  $17.00.  A  specimen  of  the  plates  and  text  sent  by  mail,  on  receipt  of  25  cts. 


HILL  ON  SYPHILIS  AND  LOCAL  CONTAGIOUS 

DISORDERS.  In  one  8vo  vol.  of  479  p.  Cloth,  $3.25. 

LSE'8  LECTURES  ON  SYPHILIS  AND  SOME 


FORMS  OF  LOCAL  DISEASE  AFFECTING 
PRINCIPALLY  THE  ORGANS  OF  GENERA- 
TION. In  one  8vo.  vol.  of  246  pages.  Cloth,  $2.25. 


26 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Venereal,  Skin. 


TAYLOR,  EGBERT  W.,  A.M.,  M.D., 

Clinical  Professor  of  Qenito  Urinaru  Diseases  in  the  College  of  Physicians  and  Surgeons,  New  York; 
Surgeon  to  the  Department  of  Venereal  and  Skin  Diseases  of  the  New  York  Hospital;  Presi- 
dent of  the  American  Dermatological  Association. 

A  Clinical  Atlas  of  Venereal  and  Skin  Diseases:  Including  Diagnosis, 
Prognosis  and  Treatment.  In  eight  large  folio  parts,  measuring  14  x  18  inches,  and 
comprising  58  beautifully-colored  plates  with  213  figures,  and  431  pages  of  text  with  85 
engravings.  Complete  work  just  ready.  Price  per  part,  $2.50.  Bound  in  one  volume, 
half  Kussia,  $27  ;  half  Turkey  Morocco,  $28.  For  sale  by  subscription  only.  Specimen 
plates  sent  on  receipt  of  10  cents.  A  full  prospectus  sent  to  any  address  on  application. 


The  completion  of  this  monumental  work  is  a 
subject  of  congratulation,  not  only  to  the  author 
and  publishers,  but  to  the  profession  at  large; 
indeed  it  is  to  the  latter  that  it  directly  appeals  as 
a  wonderlully  clear  exposition  of  a  confessedly 
difficult  branch  of  medicine.  Good  literature  has 
joined  hands  with  good  art  with  highly  satisfac- 
tory results  for  both.  There  are  altogether  213 
figures,  many  of  which  are  life  size,  and  represent 
the  highest  perfection  of  the  chromo-litho- 
graphic  art,  ana  scattered  throughout  the  text  are 
innumerable  engravings.  Quite  a  proportion  of 
these  illustrations  are  from  the  author's  own 
collection,  while  on  the  other  hand  the  best 
atlases  of  the  world  have  been  drawn  upon  for 
the  most  typical  and  successful  pictures  of  the 
many  different  types  of  venereal  and  skin  dis 
•ease.  We  think  we  may  say  without  undue 
•exaggeration  that  the  reproductions,  both  in  color 
and  in  black  and  white,  are  almost  invariably 
successful.  The  text  is  practical,  full  of  thera- 
peutical suggestions,  and  the  clinical  accounts  of 
disease  are  clear  and  incisive.  Dr.  Taylor  is, 
happily,  an  eminent  authority  in  both  departments, 
and  we  find  as  a  consequence  that  the  two  divis- 
ions of  this  work  possess  an  equal  scientific  and 
literary  merit.  We  have  already  passed  the  limits 


allotted  to  a  notice  of  this  kind,  and  while  we 
have  nothing  but  praise  for  this  admirable  atlas, 
it  must  be  said  in  justification  that  it  is  more  than 
warranted  by  the  merits  of  the  work  itself. — 
The  Medical  News,  Dec.  14, 1889. 

It  would  be  hard  to  use  words  which  would  per- 
spicuously enough  convey  to  the  reader  the  great 
value  of  this  Clinical  Atlas.  This  Atlas  is  more 
complete  even  than  an  ordinary  course  of  clinical 
lectures,  for  in  no  one  college  or  hospital  course 
is  it  at  all  probable  that  all  of  the  diseases  herein 
represented  would  be  seen.  It  is  also  more  ser- 
viceable to  the  majority  of  students  than  attend- 
ance upon  clinical  lectures,  for  most  of  the 
students  who  sit  on  remote  seats  in  the  lecture 
hall  cannot  see  the  subject  as  well  as  the  office 
student  can  examine  these  true  to-life  chromo-lith- 
ographs.  Comparing  the  text  to  a  lecturer,  it  is 
more  satisfactory  in  exactness  and  fulness  than 
he  would  be  likely  to  be  in  lecturing  over  a  single 
case.  Indeed,  this  Atlas  is  invaluable  to  the  gen- 
eral practitioner,  for  it  enables  the  eye  of  the 
physician  to  make  diagnosis  of  a  given  case  of 
skin  manifestation  by  comparing  the  case  with 
the  picture  in  the  Atlas,  where  will  be  found  also 
the  text  of  diagnosis,  pathology,  and  full  sections 
on  treatment.—  Virginia  Medical  Monthly,  Dec.  1889. 


JETYDE,  J.  NEVINS,  A.  M.,  M.  D., 

Professor  of  Dermatology  and  Venereal  Diseases  in  Rush  Medical  College,  Chicago. 

A  Practical  Treatise  on  Diseases  of  the  Skin.  For  the  use  of  Students  and 
Practitioners.  New  (second)  edition.  In  one  handsome  octavo  volume  of  676  pages, 
with  2  colored  plates  and  85  beautiful  and  elaborate  illustrations.  Cloth,  $4.50;  leather,  $5.50. 


We  can  heartily  commend  it,  not  only  as  an 
admirable  text-book  for  teacher  and  student,  but 
in  its  clear  and  comprehensive  rules  for  diagnosis, 
its  sound  and  independent  doctrines  in  pathology, 
and  its  minute  and  judicious  directions  for  the 
treatment  of  disease,  as  a  most  satisfactory  and 
complete  practical  guide  for  the  physician. — Ameri- 
can Journal  of  the  Medical  Sciences,  July,  1888. 

A  useful  glossary  descriptive  01  terms  is  given. 
The  descriptive  portions  of  this  work  are  plain 
and  easily  understood,  and  above  all  are  very 
accurate.  The  therapeutical  part  is  abundantly 
supplied  with  excellent  recommendations.  The 
picture  part  is  well  done.  The  value  of  the  work 
to  practitioners  is  great  because  of  the  excellence 
of  the  descriptions,  the  suggestiveness  of  the 
advice,  and  the  correctness  of  the  details  and  the 
principles  of  therapeutics  impressed  upon  the 
reader.—  Virginia  Med.  Monthly,  May,  1888. 


The  second  edition  of  his  treatise  is  like  his 
clinical  instruction,  admirably  arranged,  attractive 
in  diction,  and  strikingly  practical  throughout. 
The  chapter  on  general  symptomatology  is  a  model 
in  its  way;  no  clearer  description  of  the  various 
primary  and  consecutive  lesions  of  the  skin  is  to 
be  met  with  anywhere.  Those  on  general  diagno- 
sis and  therapeutics  are  also  worthy  of  careful 
study.  Dr.  Hyde  has  shown  himself  a  compre- 
hensive reader  of  the  latest  literature,  and  has  in- 
corporated into  his  book  all  the  best  of  that  which 
the  past  years  have  brought  forth.  The  prescrip- 
tions and  formulae  are  given  in  both  common  and 
metric  systems.  Text  and  illustrations  are  good, 
and  colored  plates  of  rare  cases  lend  additional 
attractions.  Altogether  it  is  a  work  exactly  fitted 
to  the  needs  of  a  general  practitioner,  and  no  one 
will  make  a  mistake  in  purchasing  it.— Medical 
Press  of  Western  New  York,  June,  1888. 


FOX,  T.,  M.  D.,  F.R.  C.  P.,  and  FOX,  T.  C.,  B.A.,  M.R.  C.S., 

Physician  to  the  Department  for  Skin  Diseases,  Physician  for  Diseases  of  the  Skin  to  the 

University  College  Hospital,  London.  Westminster  Hospital,  London. 

An  Epitome  of  Skin  Diseases.    With  Formulae.    For  Students  and  Prac- 
titioners.   Third  edition,  revised  and  enlarged.    In  one  12mo.  vol.  of  238  pp.  C!oth,  $1.25. 

manual  to  lie  upon  the  table  for  instant  reference. 
Its  alphabetical  arrangement  is  suited  to  this  use, 
for  all  one  has  to  know  is  the  name  of  the  disease, 
and  here  are  its  description  and  the  appropriate 
treatment  at  hand  and  ready  for  instant  applica- 
tion. The  present  edition  has  been  very  carefully 
revised  and  a  number  of  new  diseases  are  de- 
scribed, while  most  of  the  recent  additions  to 
dermal  therapeutics  find  mention,  and  the  formu 
lary  at  the  end  of  the  book  has  been  considerably 
augmented.— The  Medical  News,  December,  1883. 


The  third  edition  of  this  convenient  handbook 
calls  for  notice  owing  to  the  revision  and  expansion 
which  it  has  undergone.  The  arrangement  of  skin 
diseases  in  alphabetical  order,  which  is  the  method 
of  classification  adopted  in  this  work,  becomes  a 
positive  advantage  to  the  student.  The  book  is 
one  which  we  can  strongly  recommend,  not  only 
to  students  but  also  to  practitioners  who  require  a 
compendious  summary  of  the  present  state  of 
dermatology.— British  Medical  Journal,  July  2, 1883. 

We  cordially  recommend  Fox's  Epitome  to  those 
whose  time  is  limited  and  who  wish  a  handy 


WILSON,  ERASMUS,  F.  It.  S. 

The  Student's  Book  of  Cutaneous  Medicine  and  Diseases  of  the  Skin. 
In  one  handsome  small  octavo  volume  of  535  pages.     Cloth,  $3.50. 


HILLIER'S  HANDBOOK  OF  SKIN  DISEASES; 
for  Students  and  Practitioners.    Second  Ameri- 


can edition, 
with  plates. 


In  one  12mo.  volume  of  353  pages, 
Cloth,  $2.25. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Dis.  of  Women. 


27 


The'American  Systems  of  Gynecology  and  Obstetrics. 

Systems  of  Gynecology  and  Obstetrics,  in  Treatises  by  American 
Authors.  Gynecology  edited  by  MATTHEW  D.  MANN,  A.  M.,  M.  D.,  Professor  of  Obstetrics 
and  Gynecology  in  the  Medical  Department  of  the  University  of  Buffalo;  and  Obstet- 
rics edited  by  BARTON  COOKE  HIRST,  M.  D.,  Associate  Professor  of  Obstetrics  in  the 
University  of  Pennsylvania,  Philadelphia.  In  four  very  handsome  octavo  volumes,  con- 
taining 3612  pages,  1092  engravings  and  8  plates.  Complete  work  just  ready.  Per  vol- 
ume: Cloth,  $5.00;  leather,  $6.00;  half  Kussia,  $7.00.  For  safe  by  subscription  only, 
Address  the  Publishers.  Full  descriptive  circular  free  on  application. 

LIST  OF  CONTRIBUTORS. 

WILLIAM  H.  BAKER,  M.  D., 

ROBERT  BATTEY,  M.  D., 

SAMUEL  C.  BUSEY,  M.  D., 

JAMES  C.  CAMERON,  M.  D., 

HENRY  C.  COE,  A.  M.,  M.  D,, 

EDWARD  P.  DAVIS,  M.  D., 

G.  E.  DE  SCHWEINITZ,  M.  D., 

E.  C.  DUDLEY,  A.  B.,  M.  D., 

B.  McE.  EMMET,  M.  D., 

GEORGE  J.  ENGELMANN,  M.  D., 

HENRY  J.  GARRIGUES,  A.  M.,  M.  D., 

WILLIAM  GOODELL,  A.  M.,  M.  D., 

EGBERT  H.  GRANDIN,  A.  M.,  M.  D., 

SAMUEL  W.  GROSS,  M.  D., 

ROBERT  P.  HARRIS,  M.  D., 

GEORGE  T.  HARRISON,  M.  D., 

BARTON  C.  HIRST,  M.  D. 

STEPHEN  Y.  HOWELL,  M.  D., 

A.  REEVES  JACKSON,  A.  M.,  M.  D., 

W.  W.  JAGGARD,  M.  D., 

EDWARD  W.  JENKS,  M.  D.,  LL.  D., 

HOWARD  A.  KELLY,  M.  D., 
This  is  volume  two  of  The  American  System  of 
Obstetrics,  completing  the  wonderfully  full  series 
issued  from  the  house  of  Lea  Brothers  &  Co.  dur- 
ing the  past  two  years.  Two  magnificent  volumes 
devoted  to  gynecology,  and  now  two  like  volumes 
embracing  everything  pertaining  to  obstetrics. 
These  volumes  are  the  contributions  of  the  most 
eminent  gentlemen  of  this  country  in  these  de- 
partments of  the  profession.  Each  contributor 
presents  a  monograph  upon  his  special  topic, 
apparently  without  restriction  in  space,  so  that 
everything  in  the  way  of  history,  theory,  methods, 
and  results  is  presented  to  our  fullest  need.  The 


structive  in  every  direction  of  inquiry.—  The  Ob- 
stetric Gazette,  September,  1889. 

There  can  be  but  little  doubt  that  this  work  will 
find  the  same  favor  with  the  profession  that  has 
been  accorded  to  the  "System  of  Medicine  by 
American  Authors,"  and  the  "System  of  Gynecol- 
ogy byAmerican  Authors."  One  is  at  a  loss  to  know 
wnat  to  say  of  this  volume,  for  fear  that  just  and 
merited  praise  may  be  mistaken  for  flattery.  The 
subjects  of  some  of  the  papers  are  discussed  in 
various  works  on  obstetrics,  though  not  to  the  full 
extent  that  is  found  in  this  volume.  The  papers 
of  Drs.  Engelmann,  Martin,  Hirst,  Jaggard  and 
Reeve  are  incomparably  beyond  anything  that  can 
be  found  in  obstetrical  works.  Certainly  the  Edi- 


CHARLES  CARROLL  LEE,  M.  D., 
WILLIAM  T.  LUSK,  M.  D..  LL.  D., 
J.  HENDRIE  LLOYD,  M.  D., 
MATTHEW  D.  MANN,  A.  M.,  M.  D.; 
H.  NEWELL  MARTIN,  F.  R.  S.,  M.  IX, 

D.Sc.,  M.A., 

RICHARD  B.  MAURY,  M.  D., 
C.  D.  PALMER,  M.  D., 
ROSWELL  PARK,  M.  D., 
THEOPHILUS  PARVIN,  M.  D.,  LL.  D., 
R.  A.  F.  PENROSE,  M.  D.,  LL.  D., 
THADDEUS  A.  REAMY,  A.  M.,  M.  D.f 
J.  C.  REEVE,  M.  D., 
A.  D.  ROCKWELL,  A.  M.,  M.  D., 
ALEXANDER  J.  C.  SKENE,  M.  D., 
J.  LEWIS  SMITH,  M.  D., 
STEPHEN  SMITH,  M.  D., 
R.  STANSBURY  SUTTON,  A.  M.,  M.  D., 

LL.  D., 

T.  GAILLARD  THOMAS,  M.  D.,  LL.  D., 
ELY  VAN  DE  WARKER,  M.  D., 
W.  GILL  WYLIE,  M.  D. 

tor  may  be  congratulated  for  having  made  such  a 
wise  selection  of  his  contributors. — Journal  of  the 
American  Medical  Association,  Sept.  8, 1888. 

In  our  notice  of  the  "System  of  Practical  Medi- 
cine by  American  Authors,"  we  made  the  follow- 
ing statement:— "It  is  a  work  of  which  the  pro- 
fession in  this  country  can  feel  proud.  Written 
exclusively  by  American  physicians  who  are  ac- 
quainted with  all  the  varieties  of  climate  in  the 
United  States,  the  character  of  the  soil,  the  man- 
ners and  customs  of  the  people,  etc.,  it  is  pecul- 
iarly adapted  to  the  wants  of  American  practition- 
ers of  medicine,  and  it  seems  to  us  that  every  one 
of  them  would  desire  to  have  it."  Every  word 
thus  expressed  in  regard  to  the  "American  Sys- 
tem of  Practical  Medicine"  is  applicable  to  the 
"  System  of  Gynecology  by  American  Authors," 
which  we  desire  now  to  bring  to  the  attention  of 
our  readers.  It,  like  the  other,  has  been  written 
exclusively  by  American  physicians  who  are 
acquainted  with  all  the  characteristics  of  American 
people,  who  are  well  informed  in  regard  to  the 
peculiarities  of  American  women,  their  manners* 
customs,  modes  of  living,  etc.  As  every  practis- 
ing physician  is  called  upon  to  treat  diseases  of 
females,  and  as  they  constitute  a  class  to  which 
the  family  physician  must  give  attention,  and 
cannot  pass  over  to  a  specialist,  we  do  not  know  of 
a  work  in  any  department  of  medicine  that  we 
should  so  strongly  recommend  medical  men  gen- 
erally purchasing. — Cincinnati  Med.  News,  July,1887^ 


THOMAS,  T.  GAILLAKD,  M.  D.,  LL.  D., 

Professor  of  Diseases  of  Women  in  the  College  of  Physicians  and  Surgeons,  N.  F. 

A  Practical  Treatise  on  the  Diseases  of  Women.  Fifth  edition,  thoroughly 
revised  and  rewritten.  In  one  large  and  handsome  octavo  volume  of  810  pages,  with  266 
illustrations.  Cloth,  $5.00;  leather,  $6.00. 


That  the  previous  editions  of  the  treatise  of  Dr. 
Thomas  were  thought  worthy  of  translation  into 
German,  French,  Italian  and  Spanish,  is  enough 
to  give  it  the  stamp  of  genuine  merit.  At  home  it 
has  made  its  way  into  the  library  of  every  obste- 


trician and  gynaecologist  as  a  safe  guide  to  practice. 
No  small  number  of  additions  have  been  made  to 
the  present  edition  to  make  it  correspond  to  re- 
cent improvements  in  treatment. — Pacific  Medical 
and  Surgical  Journal,  Jan.  1881. 


EDIS,  ARTHUR  W.9  M.  D.,  Lond.,  F.R.  C.P.,  M.R.  C.S., 

Assist.  Obstetric  Physician  to  Middlesex  Hospital,  late  Physician  to  British  Lying-in  Hospital. 
The  Diseases  of  Women.     Including  their  Pathology,  Causation,  Symptoms, 
Diagnosis  and  Treatment.    A  Manual  for  Students  and  Practitioners.    In  one  handsome 
octavo  volume  of  576  pages,  with  148  illustrations.    Cloth,  $3.00 ;  leather,  $4.00. 


It  is  a  pleasure  to  read  a  book  so  thoroughly 
good  as  this  one.  The  special  qualities  which  are 
conspicuous  are  thoroughness  in  covering  the 
whole  ground,  clearness  of  description  and  con- 
ciseness of  statement.  Another  marked  feature  of 
the  book  is  the  attention  paid  to  the  details  of 
many  minor  surgical  operations  and  procedures, 
as,  for  instance,  the  use  of  tents,  application  of 
leeches,  and  use  of  hot  water  injections.  These 


are  among  the  more  common  methods  of  treat- 
ment, and  yet  very  little  is  said  about  them  in 
many  of  the  textbooks.  The  book  is  one  to  be 
warmly  recommended  especially  to  students  and 
general  practitioners,  who  need  a  concise  but  com- 
plete resume  of  the  whole  subject.  Specialists,  too» 
will  find  many  useful  hints  in  its  pages. — Boston 
Med.  and  Surg.  Journ.,  March  2, 1882. 


28         LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Dis.  of  Women,  Midwfy. 


EMMET,  THOMAS  ADDIS,  M.  D.,  LL.  D., 

Surgeon  to  the  Woman's  Hospital,  New  York,  etc. 

The  Principles  and  Practice  of  Gynaecology ;  For  the  use  of  Students  and 
Practitioners  of  Medicine.  New  (third)  edition,  thoroughly  revised.  In  one  large  and  very 
handsome  octavo  volume  of  880  pages,  with  150  illustrations.  Cloth,  $5 ;  leather,  $6 ; 
very  handsome  half  Kussia,  raised  bands,  $6.50. 

We  are  in  doubt  whether  to  congratulate  the 
author  more  than  the  profession  upon  the  appear- 
ance of  the  third  edition  of  this  well-known  work. 


Embodying,  as  ittioes,  the  life-long  experience  of 
one  who  has  conspicuously  distinguished  himself 
as  a  bold  and  successful  operator,  and  who  has 
devoted  so  much  attention  to  the  specialty,  we 
feel  sure  the  profession  will  not  fail  to  appreciate 


the  privilege  thus  offered  them  of  perusing  the 
views  and  practice  of  the  author.  His  earnestness 
of  purpose  and  conscientiousness  are  manifest. 
He  gives  not  only  his  individual  experience  but 


endeavors  to  represent  the  actual  state  of  gynae- 
gical science  and  art.  —  British  Medical  Jo 
M 


cological  science  and  art.  —  British  Medical  Jour- 
nal, May  16,  1885. 


TAIT,  LAWSON,  F.R.  C.  8., 

Professor  of  Gynaecology  in  Queen's  College,  Birmingham;  late  President  of  the  British  Gyne- 
cological Society ;  Fellow  American  Gynecological  Society. 

Diseases  of  Women  and  Abdominal  Surgery.  In  two  very  handsome 
octavo  volumes.  Volume  I.,  554  pages,  62  engravings  and  3  plates.  Cloth,  $3.  Now 
ready.  Volume  II.,  preparing. 


The  plan  of  the  work  does  not  indicate  the  regu- 
lar system  of  a  text  book,  and  yet  nearly  every- 
thing of  disease  pertaining  to  the  various  organs 
receives  a  fair  consideration.  The  description  of 
diseased  conditions  is  exceedingly  clear,  and  the 
treatment,  medical  or  surgical,  is  very  satisfactory. 


Much  of  the  text  is  abundantly  illustrated  with 
cases,  which  add  value  in  showing  the  results  of 
the  suggested  plans  of  treatment.  We  feel  con- 
fident that  few  gynecologists  of  the  country  will 
fail  to  place  the  work  in  their  libraries.—  The 
Obstetric  Gazette,  March,  1890. 


DAVENPORT,  F.   H.,  M.  !>., 

Assistant  in  Gynaecology  in  the  Medical  Department  of  Harvard  University,  Boston. 


De- 


Diseases  of  Women,  a  Manual  of  Non-Surgical  Gynaecology. 

signed  especially  for  the  Use  of  Students  and  General  Practitioners.     In  one  handsome 
12mo.  volume  of  317  pages,  with  105  illustrations.    Cloth,  $1.50.    Just  ready. 


We  agree  with  the  many  reviewers  whose  no- 
tices we  have  read  in  other  journals  congratulating 
Dr.  Davenport  on  the  success  which  he  has 
attained.  He  has  tried  to  write  a  book  for  the 
student  and  general  practitioner  which  would 
tell  them  just  what  they  ought  to  know  without 
distracting  their  attention  with  a  lot  of  compila- 
tions for  which  they  could  have  no  possible  use. 
In  this  he  has  been  eminently  successful.  There 
is  not  even  a  paragraph  of  useless  matter. 


Everything  is  of  the  newest,  freshest  and  moat 

Rractical,  so  much  so  that  we  have  recommended 
;  to  our  class  of  gynecology  students.  What  the 
author  advises  in  the  way  of  treatment  has  all 
been  practically  tested  by  himself,  and  each 
method  receives  only  so  much  commendation  as  he 
has  found  that  it  deserves.  We  are  sure  that 
these  good  qualities  will  command  for  it  a  large 
sale.— Canada  Medical  Record,  Dec.  1889. 


MAT,   CHARLES  H.,  M.  !>., 

Late  House  Surgeon  to  Mount  Sinai  Hospital,  New  York. 

A  Manual  of  theDiseases  of  Women.  Being  a  concise  and  systematic  expo- 
sition of  the  theory  and  practice  of  gynecoiogy.  New  (2d)  edition,  edited  by  L.  S.  Rau, 
M.  D.,  Attending  Gynecologist  at  the  Harlem* Hospital,  N.  Y.  In  one  12mo.  volume  of 
360  pages,  with  31  illustrations.  Cloth,  $1.75.  Just  ready. 


This  is  a  manual  of  gynecology  in  a  very  con- 
densed form,  and  the  fact  that  a  second  edition 
has  been  called  for  indicates  that  it  has  met  with 
a  favorable  reception.  It  is  intended,  the  author 
tells  us,  to  aid  the  student  who  after  having  care- 
fully perused  larger  works  desires  to  review  the 
subject,  and  he  adds  that  it  may  be  useful  to  the 
practitioner  who  wishes  to  refresh  his  memory 


rapidly  but  has  not  the  time  to  consult  larger 
works.  We  are  much  struck  with  the  readiness 
and  convenience  with  which  one  can  refer  to  any 
subject  contained  in  this  volume.  Carefully  com- 
piled indexes  and  ample  illustrations  also  enrich 
the  work.  This  manual  will  be  found  to  fulfil  its 
purposes  very  satisfactorily. — The  Physician  and 
Surgeon,  June,  1890. 


DUNCAN,  J.  MATTHEWS,  M.D.,  LL.  &.,  F.  R.  8.  E.,  etc. 

Clinical  Lectures  on  the  Diseases  of  Women ;  Delivered  in  Saint  Bar- 
tholomew's Hospital.    In  one  handsome  octavo  volume  of  175  pages.    Cloth,  $1.50. 

They  are  in  every  way  worthy  of  their  author  ;  I  rule,  adequately  handled  in  the  textbooks ;  others 
indeed,  we  look  upon  them  as  among  the  most    of  them,  while  bearing  upon  topics  that  are  usually 


valuable  of  his  contributions.  They  are  all  upon 
matters  of  great  interest  to  the  general  practitioner. 
Some  of  them  deal  with  subjects  that  are  not,  as  a 


treated  of  at  length  in  such  works,  yet  bear  such  a 
stamp  of  individuality  that  they  deserve  to  be 
widely  read.— N.  Y.  Medical  Journal,  March,  1880. 


HODGE  ON  DISEASES  PECULIAR  TO  WOMEN. 
Including  Displacements  of  the  Uterus.  Second 
edition,  revised  and  enlarged.  In  one  beauti- 
fully printed  octavo  volume  of  519  pages,  with 
original  illustrations.  Cloth.  $4.50. 

RAMSBOTHAM'S  PRINCIPLES  AND  PRAC- 
TICE OF  OBSTETRIC  MEDICINE  AND 
SURGERY.  In  reference  to  the  Process  of 
Parturition.  A  new  and  enlarged  edition,  thor- 
oughly revised  by  the  Author.  With  additions 
by  W.  V.  KEATING,  M.  D.,  Professor  of  Obstttrics, 


etc.,  in  the  Jefferson  Medical  Colleg  e  of  Phila- 
delphia. In  one  large  and  handsome  imperial 
octavo  volume  of  640  pages,  with  64  full  page 
plates  and  43  woodcuts  in  the  text,  containing  in 
all  nearly  200  beautiful  figures.  Strongly  bound 
in  leather,  with  raised  band?,  $7. 
WEST'S  LECTURES  ON  THE  DISEASES  OF 
WOMEN  Third  American  from  the  third  Lon- 
don edition.  In  one  octavo  volume  of  543  pages. 
Cloth,  $3.75;  leather,  $4.75. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Midwifery. 


29 


PARVIN,  THEQPHILTJS,  M.  D.,  LL.  D., 

Prof,  of  Obstetrics  and  the  Diseases  of  Women  and  Children  in  Jefferson  Med.  Coll.,  Phtta. 
The  Science  and  Art  of  Obstetrics.    New  (2d)  edition.    In  one  handsome 
3vo.  volume  of  701  pages,  with  239  engravings  and  a  colored  plate.     Cloth,  $4.25 ;  leather, 
$5.25.    Just  ready. 

The  second  edition  of  this  work  is  fully  up  to  the 
present  state  of  advancement  of  the  obstetric  art. 
The  author  has  succeeded  exceedingly  well  in 
incorporating  new  matter  without  apparently  in- 
creasing the  size  of  his  work  or  interfering  with 
the  smoothness  and  grace  of  its  literary  construc- 
tion. He  is  very  felicitous  in  his  descriptions  of 


conditions,  and  proves  himself  in  this  respect  a 
scholar  and  a  master.     Rarely  in  the  range  of 


obstetric  literature  can  be  found  a  work  which  is 
so  comprehensive  and  yet  compact  and  practical. 
In  such  respect  it  is  essentially  a  text  book  of  the 
first  merit.  The  treatment  of  the  subjects  gives  a 
real  value  to  the  work— the  individualities  of  a 
practical  teacher,  a  skilful  obstetrician,  a  close 
thinker  and  a  ripe  scholar.— Medical  Record,  Jan. 
17, 1891. 


PLAYFAIR,  W.  8.,  M.  D.,  F.  M.  C.  P., 

Professor  of  Obstetric  Medicine  in  King's  College,  London,  etc. 

A  Treatise 'on  the  Science  and  Practice  of  Midwifery.    New  (fifth) 

American,  from  the  seventh  English  edition.  Edited,  with  additions,  by  ROBERT  P.  HAB- 
BIS,  M.  D.  In  one  handsome  octavo  volume  of  664  pages,  with  207  engravings  and  5 
plates.  Cloth,  $4.00 ;  leather,  $5.00.  Just  ready. 

Truly  a  wonderful  book ;  an  epitome  of  all  ob- 
stetrical knowledge,  full,  clear  and  concise.  In 
thirteen  years  it  has  reached  seven  editions.  It 


is  perhaps  the  most  popular  work  of  its  kind  ever 
presented  to  the  profession.  Beginning  with  the 
anatomy  and  physiology  of  the  organs  concerned, 
nothing  is  left  unwritten  that  the  practical  ac- 
coucheur should  know.  It  seems  that  every 
conceivable  physiological  or  pathological  condi- 


tion from  the  moment  of  conception  to  the  time 
of  complete  involution  has  had  the  author's 
patient  attention.  The  plates  and  illustration?, 
carefully  studied,  will  teach  the  science  of  mid- 


wifery. The  reader  of  this  book  will  have  before 
him  the  very  latest  and  best  of  obstetric  practice, 
and  also  of  all  the  coincident  troubles  connected 
therewith.— Southern  Practitioner,  Dec.,  1889. 


KING,  A.  F.  A.,  M.  D., 

Professor  of  Obstetrics  and  Diseases  of  Women  in  the  Medical  Department  of  the  Columbian  Univer- 
sity, Washington,  D.  C.,  and  in  the  University  of  Vermont,  etc. 

A  Manual  of  Obstetrics.     New  (fourth)  edition.     In  one  very  handsome  12mo. 
volume  of  432  pages,  with  140  illustrations.     Cloth,  $2.50. 

Dr.  King,  in  the  preface  to  the  first  edition  of 
this  manual,  modestly  states  that  "its  purpose  is 
to  furnish  a  good  groundwork  to  the  student  at 
the  beginning  of  his  obstetric  studies."  Its  pur- 
pose is  attained ;  it  will  furnish  a  good  ground- 
work to  the  student  who  carefully  reads  it;  and 
further,  the  busy  practitioner  should  not  scorn  the 
volume  because  written  for  students,  as  it  con- 
tains much  valuable  obstetric  knowledge,  some 
of  which  is  not  found  in  more  elaborate  text- 


books.  The  chapters  on  the  anatomy  of  the 
female  generative  organs,  menstruation,  fecunda- 
tion, the  signs  of  pregnancy,  and  the  diseases  of 
pregnancy,  are  all  excellent  and  clear;  but  it  is  in 


the  description  of  labor,  both  normal  and  abnor- 
mal, that  Dr.  King  is  at  his  best.  Here  his  style 
is  so  concise,  anal  the  illustrations  are  so  good, 
that  the  veriest  tyro  could  not  fail  to  receive  a  clear 
conception  of  labor,  its  complications  and  treat- 
ment. Of  the  141  illustrations  it  may  be  safely 
said  that  they  all  illuKlrate,  and  that  the  engraver's 
work  is  excellent.  The  name  of  the  publishers 


is  a  sufficient  guarantee  that  the  work  is  pre- 
sented in  an   attractive   form,    and  from  every 


, 

standpoint  we  can  most  heartily  recommend  the 
book  both  to  practitioner  and  student.—  The  Medi- 
cal News,  Dec.  7,  1889. 


BARNES,  ROBERT,  M.  D.,  and   FANCOURT,  M.  D.9 

Phys.  to  the  General  Lying-in  Hosp.,  Lond.  Obstetric  Phys.  to  St.  Thomas1  Hosp.,  Land. 

A  System  of  Obstetric  Medicine  and  Surgery,  Theoretical  and  Clin- 
ical. For  the  Student  and  the  Practitioner.  The  Section  on  Embryology  by  Prof.  Milnes 
Marshall.  In  one  8vo.  volume  of  872  pp.,  with  231  illustrations.  Cloth,  $5 ;  leather,  $6. 


The  immediate  purpose  of  the 
handbook  of  obstetric  medic 


work  is  to  furnish 
medicine  and  surgery 
for  the  use  of  the  student  and  practitioner.  It  id 
not  an  exaggeration  to  say  of  the  book  that  it  is 
the  best  treatise  in  the  English  language  yet 
published,  and  this  will  not  be  a  surprise  to  those 
who  are  acquainted  with  the  work  of  the  elder 
Barnes.  Every  practitioner  who  desires  to  have 


inions  of  the  time  in   a 


the  best  obstetrical 
readily  accessible  anc 
own  a  coi 
Medical 

The  Authors  have  made  a  text-book  which  is  in 
every  way  quite  worthy  to  take  a  place  beside  the 
best  treatises  of  the  period.— New  York  Medical 
Journal,  July  2, 1887. 


id  condensed  form,  ought  to 
opy  of  the  book.— Journal  of  the  American 
Association,  June  12, 1886. 


BARKER,  FORDTCE,  A.  M.,  M.  D.,  LL.  D.,  Edin., 

Clinical  Professor  of  Midwifery  and  the  Diseases  of  Women  in  the  Bellevue  Hospital  Medical  College, 
New  York,  Honorary  Fellow  of  the  Obstetrical  Societies  of  London  and  Edinburgh,  etc.,  etc. 
Obstetrical  and  Clinical  Essays.     12mo.,  about  300  pages.     Preparing. 

WI1TCKEL,  F. 

A  Complete  Treatise  on  the  Pathology  and  Treatment  of  Childbed, 

For  Students  and  Practitioners.    Translated,  with  the  consent  of  the  Author,  from  the 
second  German  edition,  by  J.  R.  CHADWICK,  M.  D.    Octavo  484  pages.    Cloth,  $4.00. 


ASH  WELL'S  PRACTICAL  TREATISE  ON  THE 
DISEASES  PECULIAR  TO  WOMEN.  Third 
American  from  the  third  and  revised  London 
edition.  In  one  8vo.  vol.,  pp.  520.  Cloth,  $3.50. 

PARRY  ON  EXTRA-UTERINE  PREGNANCY: 
Its  Clinical  History,  Diagnosis,  Prognosis  aud 
Treatment.  Octavo,  272  pages.  Clotft,  $2.50. 


TANNER  ON  PREGNANCY.  Octavo,  490  pages, 
colored  plates,  16  cuts.  Cloth.  $4.25 

CHURCHILL  ON  THE  PUERPERAL  FEVER 
AND  OTHER  DISEASES  PECULIAR  TO  WO- 
MdEN.  InoneSvo.  vol.  of  464  pages.  Cloth,  $2.50. 

MEIGS  ON  THE  NATURE,  SIGNS  AND  TREAT- 
MENT OF  CHILDBED  FEVER.  In  one  8vc. 
volume  of  346  pages.  Cloth,  $2.00. 


30 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Midwfy.,  Dis.  Childn. 


SMITH,  J.  LEWIS,  M.  D., 

Clinical  Professor  of  Diseases  of  Children  in  the  Bellevue  Hospital  Medical  College,  N.  Y. 

A  Treatise  on  the  Diseases  of  Infancy  and  Childhood.  New  (seventh) 
edition,  thoroughly  revised  and  rewritten.  In  one  handsome  octavo  volume  of  881 
pages,  with  51  illustrations.  Cloth,  $4.50 ;  leather,  $5.50.  Just  ready. 

car*  ful  instructions  given  in  the  details  of  infant 
hygiene  and  the  artificial  feeding  of  infants. — 
Montreal  Medical  Journal,  Feb.  1391. 

Every  department  shows  that  it  has  been  thor- 
oughly revised,  and  that  every  advantage  has  beep 
taken  of  recent  advance  in  knowledge  to  bring  it 
completely  up  to  the  times  What  makes  the  work 
of  Dr.  Smith  of  especial  value  is  the  attention  paid 
to  diagnosis  and  the  careful  del  ail  of  treatment. 
It  is  undoubtedly  one  of  the  best  treatises  on 
children's  diseases, and  as  a  text  book  for  students 
and  guide  for  young  practitioners  it  is  unsurpassed. 
— Buffalo  Midical  and  Surgical  Journal,  Jan.  1891 

All  the  important  peitinent  facts  that  modern 
research  has  brought  to  light  are  embodied  in  the 
present  volume,  thus  bringing  it  up  to  date  and 
giving  it  the  dignity  of  ultimate  authority  upon 
the  subjects  of  which  it  treats.— New  York  Medical 
Journal,  Dec.  G,  1890. 


Notwithstanding  the  many  excellent  volumes 
that  have  been  issued  recently  on  diseases  of 
children,  the  work  of  Dr.  J.  Lewis  Smith  easily 
holds  a  front  plaie.  Its  several  editions  have  all 
been  thoroughly  revised.  In  the  present  one  we 
notice  that  many  of  the  chapters  have  been  en- 
tirely rewritten.  Full  notice  is  taken  of  all  the 
recent  advances  that  have  been  made.  As  its 
author  states  in  the  preface,  the  necessary  revision 
has  virtually  produced  anew  work.  In  the  amount 
of  information  presented  the  work  may  properly 
be  considered  to  have  doubled  in  size,  but  by 
condensation  and  the  exclusion  of  ail  obsolete 
material  the  volume  has  not  been  rendered  incon- 
veniently large.  Many  diseases  not  previously 
treated  of  have  received  special  chapters.  The 
work  is  a  very  practical  one.  Especial  care  has 
been  taken  that  the  directions  for  treatment  shall 
be  particular  and  full.  In  no  other  work  are  such 


LEISHMAN,  WILLIAM,  M.  D., 

Regius  Professor  of  Midwifery  in  the  University  of  Glasgow,  etc. 

A  System  of  Midwifery,  Including  the  Diseases  of  Pregnancy  and  the 
Puerperal  State.     Fourth  edition.     Octavo,  220  engravings.     Shortly. 

LANDIS,  HENRY  G.,  A.  M.,  M.  D., 

Professor  of  Obstetrics  and  the  Diseases  of  Women  in  Starling  Medical  College,  Columbus,  O. 

The  Management  of  Iiabor,  and  of  the  Lying-in  Period.     In  one 

handsome  12mo.  volume  of  334  pages,  with  28  illustrations.     Cloth,  $1.75. 

tempt  any  one  who  should  happen  to  commence 
the  book  to  read  it  through.  The  author  pre- 
supposes a  theoretical  knowledge  of  obstetrics, 
and  has  consistently  excluded  from  this  little 
work  everything  that  is  not  of  practical  use  in  the 
lying-in  room.  We  think  that  if  it  is  as  widely 


The  author  has  designed  to  place  in  the  hands 
of  the  young  practitioner  a  booK  in  which  he  can 
find  necessary  information  in  an  instant.  As  far 
as  we  can  see,  nothing  is  omitted.  The  advice  is 
sound,  and  the  proceedures  are  safe  and  practical. 
Centralblatt  fur  Gynakologie,  December  4,  1886. 

This  is  a  book  we  can  heartily  recommend. 


the  author  goes  much  more  practically  in 
details  of  the  management  of  labor  than 
text-books,  and  is  so  readable  throughout  as  to 


into  the 
most 


lying- 
read  as  it  deserves,  it  will  do  much  to  improve 
obstetric  practice  in  general.— New  Orleans  Medi- 
cal and  Surgical  Journal,  Mar.- 1886. 


OWEN,  EDMUND,  M.  B.,  F.  It.  C.  S., 

Surgeon  to  the  Children's  Hospital,  Great  Ormond  St.,  London. 

Surgical  Diseases  of  Children.  In  one  12mo.  volume  of  525  pages,  with  4 
chromo-lithographic  plates  and  85  woodcuts.  Cloth,  $2.  See  Series  of  Clinical  Manuals, 
page  31. 

One  is  immediately  struck  on  reading  this  book  honestly   recommended   to   both   students   and 

with  its  agreeable  style  and  the  evidence  it  every-  practitioners.      It  is  full  of  sound  information, 

where  presents  of  the  practical  familiarity  of  its  pleasantly  given.— Annals  of  Surgery,  May,  1886. 
author  with   his   subject.     The   book   may   be 


STUDENTS9  SERIES  OF  MANUALS. 

A  Series  of  Fifteen  Manuals,  for  the  use  of  Students  and  Practitioners  of  Medicine  and  Surgery, 
written  by  eminent  Teachers  or  Examiners,  and  issued  in  pocket-size  12mo  volumes  of  300-540  pages, 
richly  illustrated  and  at  a  low  price.  The  following  volumes  are  now  ready:  TREVES'  Manual  of  Sur- 
gery, by  various  writers,  in  three  volumes,  each,  $2;  BELL'S  Comparative  Physiology  and  Anatoniv,  82; 
GOULD'S  Surgical  Diagn 
peutics  (4th  edition),  J. 

PEPPER'S  Surgical  Pathology,  $2;  and 'KLEIN'S  ^Elements' of  Histology  (4th  e"ditfonj,  $1^15.     The  following 
is  in  press :    PEPPER'S  Forensic  Medicine.    For  separate  notices  see  index  on  last  page. 


SERIES  OF  CLINICAL  MANUALS. 

In  arranging  for  this  Series  it  has  been  the  design  of  the  publishers  to  provide  the  profession  with 
a  collection  of  authoritative  monographs  on  important  clinical  subjects  in  a  cheap  and  portable  form. 
The  volumes  will  contain  about  550  pages  and  will  be  freely  illustrated  by  chromo-lithographs  and  wood- 
cuts. The  following  volumes  are  now  ready:  YEO  on  Food  in  Health  and  Disease,  $2;  BROADBENT  on 
the  Pulse,  $1.75;  CARTER  &  FROST'S  Ophthalmic  Surgery,  8225;  HUTCHINSON  on  Syphilis,  82.25;  BALL  on 
the  Rectum  and  Anus,  82.25;  MARSH  on  the  Joints,  82;  OWEN  on  Surgical  Diseases  of  Children,  82; 
MORRIS  on  Surgical  Diseases  of  the  Kidney,  82.25 ;  PICK  on  Fractures  and  Dislocations,  82 ;  BUTLIN  on 
the  Tongue,  83.50;  TREVES  on  Intestinal  Obstruction,  82;  and  SAVAGE  on  Insanity  and  Allied  Neuroses,  82. 
The  following  is  in  active  preparation:  LUCAS  on  Diseases  of  the  Urethra.  For  separate  notices  see 
index  on  last  page. 


CONDIE'S  PRACTICAL  TREATISE  ON  THE 
DISEASES  OF  CHILDREN.  Sixth  edition,  re- 
vised and  augmented.  In  one  octavo  volume  of 
779  pages.  Cloth,  85.25;  leather,  86.25. 


WEST  ON  SOME  DISORDERS  OF  THE  NERV- 
OUS SYSTEM  IN  CHILDHOOD.  In  one  small 
12mo.  volume  of  127  pages.  Cloth,  81.00. 


LEA  BROTHERS  &  Co.'s  PUBLICATIONS — Med.  Juris.,  Miscel. 


31 


TIDY,  CHARLES  METMOTT,  M.  B.,  F.  C.  8., 

Professor  of  Chemistry  and  of  Forensic  Medicine  and  Public  Health  at  the  London  Hospital,  etc. 
Legal  Medicine.     VOLUME  II.     Legitimacy  and  Paternity,  Pregnancy,  Abor- 
tion, Rape,  Indecent  Exposure,  Sodomy,  Bestiality,  Live  Birth,  Infanticide,  Asphyxia, 
Drowning,  Hanging,  Strangulation,  Suffocation.    Making  a  very  handsome  imperial  oc- 
tavo volume  of  529  pages.    Cloth,  $6.00 ;  leather,  $7.00. 

VOLUME  I.    Containing   664    imperial  octavo  pages,  with  two  beautiful  colored 
plates.    Cloth,  $6.00;  leather,  $7.00. 
The  satisfaction  expressed  with  the  first  portion 


of  this  work  is  in  no  wise  lessened  by  a  perusal  of 
the  second  volume.  We  find  it  characterized  by 
the  same  fulness  of  detail  and  clearness  of  ex- 
pression which  we  had  occasion  so  highly  to  com- 
mend in  our  former  notice,  and  which  render  it  so 
valuable  to  the  medical  jurist.  The  copious 


tables  of  cases  appended  to  each  division  of  the 
subject  must  have  cost  the  author  a  prodigious 
amount  of  labor  and  research,  but  they  constitute 
one  of  the  most  valuable  features  of  the  book, 
especially  for  reference  in  medico-legal  trials.— 
American  Journal  of  the  Medical  Sciences,  April,  1884. 


TAYLOR,  ALFRED  8.,  M.  !>., 

Lecturer  on  Medical  Jurisprudence  and  Chemistry  in  Ghiy's  Hospital,  London. 

Poisons  in  Relation  to  Medical  Jurisprudence  and  Medicine.  Third 
American,  from  the  third  and  revised  English  edition.  In  one  large  octavo  volume  of  788 
pages.  Cloth,  $5.50 ;  leather,  $6.50. 


By  the  Same  Author. 

A  Manual  of  Medical  Jurisprudence.  Eighth  American  from  the  tenth  Lon- 
don edition,  thoroughly  revised  and  rewritten.  Edited  by  JOHN  J.  REESE,  M.  D.  In  one 
large  octavo  volume. 

PEPPER,  AUGUSTUS  J.,  M.  8.,  M.  B.,  F.  R.  C.  S.9 

Examiner  in  Forensic  Medicine  at  the  University  of  London. 

Forensic  Medicine.  In  one  pocket-size  12mo.  volume.  Preparing.  See  Students1 
Series  of  Manuals,  below. 

LEA,  HENRY  C.,  LL.  I>. 

Chapters  from  the  Religious  History  of  Spain. — Censorship  of  the 
Press. — Mystics  and  Illuminati. — The  Endemoniadas. — El  Santo  Nino 
de  la  Guardia. — Brianda  de  Bardaxi.  In  one  12mo.  volume  of  522 
Cloth,  $2.50.  Just  ready. 

The  width,  depth  and  thoroughness  of  research 
which  have  earned  Dr.  Lea  a  high  European  place 


Inquisition  has  yet 
10  side- issues  of  that 


as  the  ablest  historian  the 

found  are  here  applied  to  some  side-ii 

great  subject.    We  have  only  to  say  of  this  volume 

that  it  worthily  complements  the  author's  earlier 

studies  in  ecclesiastical  history.     His  extensive 

and  minute  learning,  much  of  it  from  inedited 

manuscripts  in  Mexico,  appears  on  every  page. — 

London  Antiquary,  Jan.  Ih91. 

After  attentively  reading  the  work  one  does  not 
know  whether  the  author  is  a  Catholic,  a  Protestant 


or  a  free-thinker.  This  moderation  deprives  the 
indictment  of  none  of  its  force.  The  facts  and 
the  documents,  of  which  the  number  and  novelty 
attest  a  patient  erudition,  are  grouped  in  luminous 
order  and  produce  on  the  reader  an  effect  all  the 
more  powerful  in  that  it  seems  the  less  designed. 
When  we  add  that  the  style  is  in  every  way  excel- 
lent, that  it  is  clear,  sober  and  precise,  we  do  full 
justice  to  a  work  which  reflects  the  highest  honor 
on  the  talents  of  the  writer  and  on  the  method  of 
the  modern  school  of  history.— Revue  Critique 
d'Histoire  et  de  Litterature,  Paris,  Jan.  1891. 


By  the  same  Author. 

Superstition  and  Force :  Essays  on  The  Wager  of  Law.  The  Wager  of 
Battle,  The  Ordeal  and  Torture.  Third  revised  and  enlarged  edition.  In  one 
handsome  royal  12mo.  volume  of  552  pages.  Cloth,  $2.50. 

"  si?,  the  breadth  and  accuracy  of  his  researches 
among  the  rarer  sources  of  knowledge,  the  gravity 
and  temperance  of  his  statements,  combined  with 


Mr.  Lea's  curious  historical  monographs,  of 
which  one  of  the  most  important  is  here  produced 
in  an  enlarged  form,  have  given  him  a  unique 
position  among  English  and  American  scholars. 
He  is  distinguished  for  his  recondite  and  affluent 
learning,  his  power  of  exhaustive  historical  analy- 


singular  earnestness  of  conviction,  and  his  warm 
attachment  to  the  cause  of  freedom  and  intellect- 
ual progress.— JV.  Y.  Tribune,  August  9,  1878. 


By  the  Same  Author. 

Studies  in  Church  History.  The  Rise  of  the  Temporal  Power— Ben- 
efit of  Clergy— Excommunication— The  Early  Church  and  Slavery.  Sec- 
ond and  revised  edition.  In  one  royal  octavo  volume  of  605  pages.  Cloth,  $2.50. 


The  author  is  preeminently  a  scholar;  he  takes 
up  every  topic  allied  with  the  leading  theme  and 
traces  it  out  to  the  minutest  detail  with  a  wealth 
of  knowledge  and  impartiality  of  treatment  that 
compel  admiration.  The  amount  of  information 
compressed  into  the  book  is  extraordinary,  and 
the  profuse  citation  of  authorities  And  references 
makes  the  work  particularly  valuable,  to  the  student 
who  desires  an  exhaustive  review  from  original 
sources.  In  no  other  single  volume  is  the  develop- 
ment of  the  primitive  church  traced  with  so  much 
clearness  and  with  so  definite  a  perception  of 
complex  or  conflicting  forces. — Boston  TrnvtUer. 

Mr.  Lea  is  Jacile  prinr.eps  among  American 
scholars  in  the  history  of  the  Middle  Ages,  and, 
indeed,  we  know  of  no  European  writer  who  nas 


shown  such  research,  accuracy  and  grasp  in 
investigating  important  and  out-of-the-way  topics 
connected  with  th«  history  of  Europe  in  the  Mid- 
dle Ages.— N.  Y.  Times. 

It  is  some  years  since  we  read  the  first  edition 
of  this  work  by  Mr.  Lea,  and  the  impression  made 
by  it  on  us  at  the  time  is  confirmed  by  reperusa! 
ol  it  in  this  enlarged  and  improved  form ;  namely, 
that  it  is  a  book  of  great  research  and  accuracy, 
full  of  varied  information  on  very  interesting 
phases  of  church  life  and  history.  It  discusses 
each  subject  with  a  rare  fulness  of  dates  and  in- 
stances, and  a  curious  conscientiousness  of  veri- 
fication and  citation  cf  authorities.— Edinburgh 
Scotsman. 


Allen's  Anatomy  .... 

American  Journal  of  the  Medical  Sciences 

American  Systems  of  Gynecology  and  Obstetri 

American  System  of  Practical  Medicine . 

American  System  of  Dentistry 

A  shhurst's  Surgery       .... 

Ashwell  on  Diseases  of  Women 

Airfield's  Chemistry     .... 

Ball  on  the  Rectum  and  Anus 

Barker's  Obstetrical  and  Clinical  Essays, 

Barlow's  Practice  of  Medicine 

Barnes'  System  of  Obstetric  Medicine 

Bartholow  on  Electricity 

Basham  on  Renal  Diseases    .          . 

Bell's  Comparative  Physiology  and  Anatomy 

Bellamy's  Surgical  Anatomy 

Berry  on  the  Eye  .... 

Billings'  National  Medical  Dictionary     . 

Blandford  on  Insanity 

Bloxam's  Chemistry      .... 

Bristowe's  Practice  of  Medicine 

Broadbent  on  the  Pulse 

Browne  on  Koch's  Remedy  . 

Browne  on  the  Throat,  Nose  and  Ear 

Bruce's  Materia  Medica  and  Therapeutics 

Brunton's  Materia  Medica  and  Therapeutics 

Bryant's  Practice  of  Surgery  . 

Bumstead  and  Taylor  on  Venereal.    See  Taylo 

Burnett  on  the  Ear        .... 

Butlin  on  the  Tongue    .... 

Carpenter  on  the  Use  and  Abuse  of  Alcohol 

Carpenter's  Human  Physiology 

Carter  &  Frost's  Ophthalmic  Surgery 

Chambers  on  Diet  and  Regimen 

Chapman's  Human  Physiology 

Charles'  Physiological  and  Pathological  Chem 

Churchill  on  Puerperal  Fever 

Clarke  and  Lockwood's  Dissectors'  Manual 

Classen's  Quantitative  Analysis 

Cleland's  Dissector        .... 

Clouston  on  Insanity    . 

Clowes'  Practical  Chemistry 

Coats'  Pathology  . 

Cohen  on  the  Throat     .... 

Coleman's  Dental  Surgery 

Condie  on  Diseases  of  Children 

Cornil  on  Syphilis          .... 

Dalton  on  the  Circulation 

Dalton's  HumanPhysiology 

Davenport  on  Diseases  of  Women  . 

Davis'  Clinical  Lectures 

Draper's  Medical  Physics 

Druitt's  Modern  Surgery 

Duncan  on  Diseases  of  Women 

Dungllson's  Medical  Dictionary 

Edes'  Materia  Medica  and  Therapeutics 

Edis  on  Diseases  of  Women  . 

Ellis'  Demonstrations  of  Anatomy 

Emmet's  Gynaecology 

Erichsen's  System  or  Surgery 

Farquharson's  Therapeutics  and  Mat.  Med. 

Finlayson's  Clinical  Diagnosis 

Flint  on  Auscultation  and  Percussion 

Flint  on  Phthisis  .... 

Flint  on  Respiratory  Organs 

Flint  on  the  Heart         .... 

Flint's  Essays      ..... 

Flint's  Practice  of  Medicine 

Folsom's  Laws  of  U.  S.  on  Custody  of  Insane 

Foster's  Physiology       .... 

Fothergill's  Handbook  of  Treatment 

Fownes'  Elementary  Chemistry      .          . 

Fox  on  Diseases  of  the  Skin  . 

Frankland  and  Japp's  Inorganic  Chemistry 

Fuller  on  the  Lungs  and  Air  Passages     . 

Gant's  Student's  Surgery 

Gibbes'  Practical  Pathology 

Gibney's  Orthopaedic  Surgery 

GouldTs  Surgical  Diagnosis     . 

Gray's  Anatomy 

Gray  on  Nervous  Diseases      . 

Greene's  Medical  Chemistry  . 

Green's  Pathology  and  Morbid  Anatomy 

Griffith's  Universal  Formulary 

Gross  on  Foreign  Bodies  in  Air-Passages 

Gross  on  Impotence  and  Sterility    . 

Gross  on  Urinary  Organs 

Gross  System  or  Surgery 

Habershon  on  the  Abdomen 

Hamilton  on  Fractures  and  Dislocations 

Hamilton  on  Nervous  Diseases 

Hare's  Practical  Therapeutics 

Hartshorne's  Anatomy  and  Physiology  . 

Hartshorne's  Conspectus  of  thelHed.  Science 

Hartshorne's  Essentials  of  Medicine 

Hermann's  Experimental  Pharmacology 


8,i 


Hill  on  Syphilis 

Hillier's  Handbook  of  Skin  Diseases 

Hoblyn's  Medical  Dictionary 

Hodge  on  Women 

Hoffmann  and  Power's  Chemical  Analysis 

Holden's  Landmarks    .... 

Holland's  Medical  Notes  and  Reflections 

Holmes'  Principles  and  Practice  of  Surgery 

Holmes' System  of  Surgery 

Horner's  Anatomy  and  Histology 

Hudson  on  Fever 

Hutchinson  on  Syphilis 


24 

7,30 


Hyde  on  the  Diseases  of  the  Skin    . 

Jones  (C.  Handfield)  on  Nervous  Disorders 

Juler's  Ophthalmic  Science  and  Practice 

King's  Manual  of  Obstetrics  . 

Klein's  Histology         i»vl  >t  I  t  .=  **t    .*  »,  » 

Landis  on  Labor 

La  Roche  on  Pneumonia,  Malaria,  eic. 

La  Roche  on  Yellow  Fever    . 

Laurence  and  Moon's  Ophthalmic  Surgery 

Lawson  on  the  Eye,  Orbit  and  Eyelid 

Lea's  Chapters  from  Reli  ' 


Lea's  Studies  in  Church  History 

Lea's  Superstition  and  Force 

Lee  on  Syphilis    .... 

Lehmann^s  Chemical  Physiology    . 

Leishman's  Midwifery 

Lucas  on  Diseases  of  the  Urethra  . 

Ludlow's  Manual  of  Examinations 

Lyons  on  Fev  er  . 

Maisch's  Organic  Materia  Medica  . 

Marsh  on  the  Joints  . 

May  on  Diseases  of  Women   . 


J8  t  Medical  News 

18    Medical  News  Visiting  List  . 


2,30 


1,30 


3,30 
17 


29 

6,30 
10 
6 
19 
10 
13 
18 
24 


27 


Medical  News  Physicians'  Ledger  . 
Meigs  on  Childbed  Fever 
Miller's  Practice  of  Surgery 


dney 


Miller's  Principles  of  Surgery 
Morris  on  Diseases  of  the  Ki 


Mo 

National  Dispensatory 


age  on  Insanity,  including  Hysteria 
arer's  Essentials  of  Histology, 


18 


25 


28 


22 


25,30 


National  Medical  Dictionary 

Neill  and  Smith's  Compendium  of  Med.  Sci. 

Nettleship  on  Diseases  of  the  Eye  . 

Norris  and  Oliver  on  the  Eye 

Owen  on  Diseases  of  Children 

Parrish's  Practical  Pharmacy 

Parry  on  Extra-Uterine  Pregnancy 

Parvin's  Midwifery 

Pavy  on  Digestion  and  its  Disorders 

Payne's  General  Pathology    . 

Pepper's  System  of  Medicine 

Pepper's  Forensic  Medicine  . 

Pepper's  Surgical  Pathology 

Pick  on  Fractures  and  Dislocations 

Pirrie's  System  of  Surgery    . 

Playfair  on  Nerve  Prostration  and  Hyst  ria 

Playfair's  Midwifery     . 

Power's  Human  Physiology  .          •       «.     . 

Purdy  on  Bright's  Disease  and  Allied  A  ff  ction 

Ralfe's  Clinical  Chemistry 

Ramsbotham  on  Parturition  . 

Remsen's  Theoretical  Chemistry    . 

Reynolds'  System  of  Medicine 

Richardsonrs  Preventive  Medicine 

Roberts  on  Urinary  Diseases 

Roberts'  Compend  of  Anatomy     . 

Roberts'  Surgery 

Robertson's  Physiological  Physics 

Ross  on  Nervous  Diseases 

Schafer's  Essentia 

Schreiber  on  Massage  . 

Seller  on  the  Throat.  Nose  and  Naso-Ph  rynx 

Senn's  Surgical  Bacteriology 

Series  of  Clinical  Manuals 

Simon's  Manual  of  Chemistry 

Blade  on  Diphtheria 

Smith  (Edward)  on  Consumption 

Smith  ( J.  Lewis)  on  Children 

Smith's  Operative  Surgery     . 

Stille  on  Cholera  .... 

Still<§  &  Maisch's  National  Dispensatory 

Stille's  Therapeutics  and  Materia  Medica 

Stimson  on  Fractures  and  Dislocations 

Stimson's  Operative  Surgery 

Students'  Series  of  Manuals  . 

Sturges'  Clinical  Medicine 

Tait's  Diseases  of  Women  and  Abdom.  Surge 

Tanner  on  Signs  and  Diseases  of  Pregnancy 

Tanner's  Manual  of  Clinical  Medicine     . 

Taylor's  Atlas  of  Venereal  and  Skin  Disease 

Taylor  on  Venereal  Diseases 

Taylor  on  Poisons         .... 

Taylor's  Medical  Jurisprudence      . 

Thomas  on  Diseases  of  Women 

Thompson  on  Stricture 

Thompson  on  Urinary  Organs 

Tidy's  Legal  Medicine . 

Todd  on  Acute  Diseases 

Treves'  Manual  of  Surgery    . 

Treves'  Surgical  Applied  Anatomy 

Treves  on  Intestinal  Obstruction    .          . 

Tuke  on  the  Influence  of  Mind  on  the  Body 


26 
1» 
23 
29 

3,30 
30 
17 
16 
23 
23 
31 
31 
31 


24,30 
3 

19 
11 

1.80 
28 
1 
3 
3 
29 
21 
21 

24,30 
12 


Vaughan  &  Novy's  Ptomaines  and  Leucoma    ea    16 
Visiting  List,  The  Medical  News     . 
Walshe  on  the  Heart    .... 
Watson's  Practice  of  Physic  .          .          •  ]£ 

Wells  on  the  Eye  .... 

West  on  Diseases  of  Women  .          . 

West  on  Nervous  Disorders  in  Childhood 
Williams  on  Consumption     .          . 
Wilson's  Handbook  of  Cutaneous  Medicine 
Wilson's  Human  Anatomy   .          .    _•.... 
Winckel  on  Pathol.  and  Treatment  of  Childbed 
Wohler's  Organic  Chemistry 
Woodhead's  Practical  Pathology    .          - 
Year-Books  of  Treatment  for  1886.  '87,  '89  and  '90^  17 
Yeo  on  Food  in  Health  and  Disease         .          .  1<,30 


23 
30 
11 
29 
29 
17 
13 
15 

30,31 
18,30 
22,30 
21 
19 
29 

8.30 
24 

10,30 
28 
10 
14 
17 
24 
7 

20 

7,30 
19 

19,30 
13 
17 
18 
IS 
4 
8 
17 
17 
30 


27 
24 
24 
31 

17 

21,30 

6,30 

21,30 

19 


LEA   BROTHERS   &   CO.,    Philadelphia. 


TVEKSITY  OF  0 


YC  88487 


